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Sample records for localised resectable neuroblastoma

  1. Treatment of localised resectable neuroblastoma. Results of the LNESG1 study by the SIOP Europe Neuroblastoma Group

    NARCIS (Netherlands)

    de Bernardi, B.; Mosseri, V.; Rubie, H.; Castel, V.; Foot, A.; Ladenstein, R.; Laureys, G.; Beck-Popovic, M.; de Lacerda, A. F.; Pearson, A. D. J.; de Kraker, J.; Ambros, P. F.; de Rycke, Y.; Conte, M.; Bruzzi, P.; Michon, J.

    2008-01-01

    Main objective of this study was to confirm that surgery alone is an effective and safe treatment for localised resectable neuroblastoma except stage 2 with amplified MYCN gene (MYCNA). Of 427 eligible stages 1-2 patients, 411 had normal MYCN and 16 had MYCNA. Of the 288 stage 1 patients with normal

  2. Neuroblastoma: treatment outcome after incomplete resection of primary tumors.

    Science.gov (United States)

    Moon, Suk-Bae; Park, Kwi-Won; Jung, Sung-Eun; Youn, Woong-Jae

    2009-09-01

    For International Neuroblastoma Staging System (INSS) stages III or IV neuroblastoma (intermediate or high risk), complete excision of the primary tumor is not always feasible. Most current studies on the treatment outcome of these patients have reported on the complete excision status. The aim of this study is to review the treatment outcome after the incomplete resection. The medical records of 37 patients that underwent incomplete resection between January 1986 and December 2005 were reviewed retrospectively. Incomplete resection was assessed by review of the operative notes and postoperative computerized tomography. Age, gender, tumor location, INSS stage, N-myc gene copy number, pre- and postoperative therapy, and treatment outcome were reviewed. The treatment outcome was evaluated according to the postoperative treatment protocol in the high-risk group. Intermediate-risk patients were treated with conventional chemotherapy, isotretinoin (ITT) and interleukin-2 (IL-2). High-risk patients were treated with peripheral blood stem cell transplantation (PBSCT), ITT, and IL-2 (N = 11). Before the introduction of PBSCT, the high-risk patients were also treated with the conventional chemotherapy (N = 19). Intermediate-risk patients (N = 5) currently have no evidence of disease (NED). For the high-risk patients (N = 32), 19 patients were treated with chemotherapy alone; 15 patients died of their disease while four patients currently have an NED status. Eight of 11 patients that underwent PBSCT are currently alive. For intermediate risk, conventional chemotherapy appears to be acceptable treatment. However, for high-risk patients, every effort should be made to control residual disease including the use of myeloablative chemotherapy, differentiating agents and immune-modulating agents.

  3. Is complete resection of high-risk stage IV neuroblastoma associated with better survival?

    Science.gov (United States)

    Yeung, Fanny; Chung, Patrick Ho Yu; Tam, Paul Kwong Hang; Wong, Kenneth Kak Yuen

    2015-12-01

    The role of surgery in the management of stage IV neuroblastoma is controversial. In this study, we attempted to study if complete tumor resection had any impact on event-free survival (EFS) and overall survival (OS). A retrospective analysis of patients with stage IV neuroblastoma between November 2000 and July 2014 in a tertiary referral center was performed. Demographics data, extent of surgical resection, and outcomes were analyzed. A total of 34 patients with stage IV neuroblastoma according to International Neuroblastoma Staging System (INSS) were identified. The median age at diagnosis and operation was 3.5 (±1.9) years and 3.8 (±2.0) years, respectively. Complete gross tumor resection (CTR) was achieved in twenty-four patients (70.1%), in which one of the patients had nephrectomy and another had distal pancreatectomy. Gross total resection (GTR) with removal of >95% of tumor was performed in six patients (17.6%) and subtotal tumor resection (STR) with removal of >50%, but <95% of tumor was performed in four patients (11.8%). There was no statistical significance in terms of 5-year EFS and OS among the 3 groups. There was no surgery-related mortality or morbidity. From our center's experience, as there was no substantial survival benefit in stage IV neuroblastoma patients undergoing complete tumor resection, organ preservation and minimalization of morbidity should also be taken into consideration. Copyright © 2015. Published by Elsevier Inc.

  4. Complete surgical resection improves outcome in INRG high-risk patients with localized neuroblastoma older than 18 months.

    Science.gov (United States)

    Fischer, Janina; Pohl, Alexandra; Volland, Ruth; Hero, Barbara; Dübbers, Martin; Cernaianu, Grigore; Berthold, Frank; von Schweinitz, Dietrich; Simon, Thorsten

    2017-08-04

    Although several studies have been conducted on the role of surgery in localized neuroblastoma, the impact of surgical timing and extent of primary tumor resection on outcome in high-risk patients remains controversial. Patients from the German neuroblastoma trial NB97 with localized neuroblastoma INSS stage 1-3 age > 18 months were included for retrospective analysis. Imaging reports were reviewed by two independent physicians for Image Defined Risk Factors (IDRF). Operation notes and corresponding imaging reports were analyzed for surgical radicality. The extent of tumor resection was classified as complete resection (95-100%), gross total resection (90-95%), incomplete resection (50-90%), and biopsy (Neuroblastoma Risk Group (INRG) staging system. Survival curves were estimated according to the method of Kaplan and Meier and compared by the log-rank test. A total of 179 patients were included in this study. 77 patients underwent more than one primary tumor operation. After best surgery, 68.7% of patients achieved complete resection of the primary tumor, 16.8% gross total resection, 14.0% incomplete surgery, and 0.5% biopsy only. The cumulative complication rate was 20.3% and the surgery associated mortality rate was 1.1%. Image defined risk factors (IDRF) predicted the extent of resection. Patients with complete resection had a better local-progression-free survival (LPFS), event-free survival (EFS) and OS (overall survival) than the other groups. Subgroup analyses showed better EFS, LPFS and OS for patients with complete resection in INRG high-risk patients. Multivariable analyses revealed resection (complete vs. other), and MYCN (non-amplified vs. amplified) as independent prognostic factors for EFS, LPFS and OS. In patients with localized neuroblastoma age 18 months or older, especially in INRG high-risk patients harboring MYCN amplification, extended surgery of the primary tumor site improved local control rate and survival with an acceptable risk of

  5. Influence of image-defined risk factors on the outcome of patients with localised neuroblastoma. A report from the LNESG1 study of the European International Society of Paediatric Oncology Neuroblastoma Group.

    Science.gov (United States)

    Monclair, Tom; Mosseri, Véronique; Cecchetto, Giovanni; De Bernardi, Bruno; Michon, Jean; Holmes, Keith

    2015-09-01

    The European multicenter study LNESG1 was designed to evaluate the safety and efficacy of surgical treatment alone in patients with localised neuroblastoma. In a retrospective, observational study we examined the impact of image-defined risk factors (IDRF) on operative complications and survival (EFS and OS). 534 patients with localised, non-MYCN amplified neuroblastoma were recruited between 1995 and 1999. Group 1 consisted of 291 patients without IDRF (Stage L1 in the International Neuroblastoma Risk Group (INRG) staging system), all treated with primary surgery. Group 2: 118 patients with IDRF (INRG Stage L2), also treated with primary surgery. Group 3: 125 patients in whom primary surgery was not attempted, 106 receiving neo-adjuvant chemotherapy. In L1 patients (Group 1) 5-year EFS was 92% and OS 98%. In L2 patients (Group 2 and 3) EFS was 79% and OS 89%. The differences in both EFS and OS were significant. EFS and OS in Group 2 (86% and 95%) were significantly better than 73% and 83% in Group 3. In INSS stage 1, 2 and 3, EFS were respectively 94%, 81% and 76%. Except between stage 2 and 3 the differences were significant. OS were respectively 99%, 93% and 83%, all significantly different. The 17% operative complication rate in L2 patients was significantly higher than 5% in L1 patients. In localised neuroblastoma, IDRF at diagnosis are associated with worse survival rates and higher rates of operative complications. The impact of IDRF should become an integrated part of therapy planning. © 2015 Wiley Periodicals, Inc.

  6. Neuroblastoma

    International Nuclear Information System (INIS)

    Hall-Craggs, M.A.; Finn, J.P.; Dicks-Mireaux, C.; Kiely, E.M.; Pritchard, J.

    1989-01-01

    Twenty-one children with neuroblastoma (mean age, 36.7 months) were examined with high-field strength (1.5 T) MR imaging to define how accurately disease could be documented and to establish optimum sequences. Twenty-eight studies were obtained with T1- and T2-weighted spin-echo and short inversion-recovery (STIR) sequences. Thirteen children underwent surgery, 16 CT. MR imaging exactly predicted tumor extent and involvement of adjacent organs, vessels, and the spine in all patients undergoing surgery. STIR images defined tumor margins and node involvement most clearly. Following chemotherapy, MR imaging could not differentiate active tumor from maturing ganglioneuroma or residual hyperplasia. MR imaging was superior to CT in assessing intraabdominal, marrow, and spinal disease

  7. First Delayed Resection Findings After Irreversible Electroporation (IRE) of Human Localised Renal Cell Carcinoma (RCC) in the IRENE Pilot Phase 2a Trial

    Energy Technology Data Exchange (ETDEWEB)

    Wendler, Johann Jakob, E-mail: johann.wendler@med.ovgu.de [Otto von Guericke University of Magdeburg, Department of Urology, University Hospital (Germany); Ricke, Jens, E-mail: jens.Ricke@med.ovgu.de; Pech, Maciej, E-mail: macej.pech@med.ovgu.de; Fischbach, Frank, E-mail: frank.fischbach@med.ovgu.de; Jürgens, Julian, E-mail: julian.juergens@med.ovgu.de [University of Magdeburg, Department of Radiology (Germany); Siedentopf, Sandra, E-mail: sandra.siedentopf@med.ovgu.de; Roessner, Albert, E-mail: albert.roessner@med.ovgu.de [University of Magdeburg, Institute of Pathology (Germany); Porsch, Markus, E-mail: markus.porsch@med.ovgu.de; Baumunk, Daniel, E-mail: daniel.baumunk@med.ovgu.de; Schostak, Martin, E-mail: martin.schostak@med.ovgu.de [Otto von Guericke University of Magdeburg, Department of Urology, University Hospital (Germany); Köllermann, Jens, E-mail: jens.koellermann@sana.de [Sana Klinikum Offenbach Am Main, Institute of Pathology (Germany); Liehr, Uwe-Bernd, E-mail: uwe-bernd.liehr@med.ovgu.de [Otto von Guericke University of Magdeburg, Department of Urology, University Hospital (Germany)

    2016-02-15

    IntroductionIt is postulated that focal IRE affords complete ablation of soft-tissue tumours while protecting the healthy peritumoral tissue. Therefore, IRE may be an interesting option for minimally invasive, kidney-tissue-sparing, non-thermal ablation of renal tumours.AimWith this current pilot study (“IRENE trial”), we present the first detailed histopathological data of IRE of human RCC followed by delayed tumour resection. The aim of this interim analysis of the first three patients was to investigate the ablation efficiency of percutaneous image-guided focal IRE in RCC, to assess whether a complete ablation of T1a RCC and tissue preservation with the NanoKnife system is possible and to decide whether the ablation parameters need to be altered.MethodsFollowing resection 4 weeks after percutaneous IRE, the success of ablation and detailed histopathological description were used to check the ablation parameters.ResultsThe IRE led to a high degree of damage to the renal tumours (1 central, 2 peripheral; size range 15–17 mm). The postulated homogeneous, isomorphic damage was only partly confirmed. We found a zonal structuring of the ablation zone, negative margins and, enclosed within the ablation zone, very small tumour residues of unclear malignancy.ConclusionAccording to these initial, preliminary study results of the first three renal cases, a new zonal distribution of IRE damage was described and the curative intended, renal saving focal ablation of localised RCC below <3 cm by percutaneous IRE by the NanoKnife system appears to be possible, but needs further, systematic evaluation for this treatment method and treatment protocol.

  8. A case of neonatal neuroblastoma

    International Nuclear Information System (INIS)

    Nounaka, Osamu; Gotoh, Toshiaki; Takahashi, Kazuaki; Koyanagi, Tomohiko; Kakizaki, Hidehiro; Nakanishi, Shoichiro.

    1987-01-01

    A two-day-old male infant was referred to us for probable neuroblastoma, because of upper abdominal mass and positive urinary vanillylmandelic acid (VMA). Primary site of neuroblastoma was not found, but clinically IV-S stage neuroblastoma was strongly suspected, so 131 I-metaiodobenzylguanidine (MIBG) scan was performed. RI accumulation was found near the left adrenal region. Thus laparotomy was performed and left adrenal was resected. Liver biopsy was also performed. Microscopically multiple in situ foci of neuroblastoma cells were found in the left adrenal and tumor involvement was also seen in the liver. Skin and bone marrow metastasis were ruled out. Minimal chemotherapy was intended but abandoned soon because of possible spontaneous regression of stage IV-S neuroblastoma. Thereafter liver has been getting smaller and the patient has been doing well. Urinary VMA and homovanillic acid (HVA) per creatinine, which were used for follow-up, have also normalized after 3 months. Treatment of stage IV-S neuroblastoma and early diagnosis by 131 I-MIBG scan were reviewed. (author)

  9. Multidisciplinary management of cervical neuroblastoma in infants.

    Science.gov (United States)

    Csanády, Miklós; Vass, Gábor; Bartyik, Katalin; Majoros, Valéria; Rovó, László

    2014-12-01

    Neuroblastoma is the most common malignancy in infancy, it is a histologically and genetically heterogeneous tumor, the therapy and outcome of which is influenced by age, histological variant and genetic background as well. We present two consecutive infant patients with neuroblastoma of the neck discussing the etiology, the diagnosis and the surgical and oncological treatment of the tumor, which was observed in a relatively rare manifestation in the head-neck region. Our first patient (age: 5.5 months) was MYCN (v-myc myelocytomatosis viral related oncogene, neuroblastoma derived) negative, INSS (International Neuroblastoma Staging System) Stage 3 and INRGSS (International Neuroblastoma Risk Group Staging System) Stage 3 because of the contralateral lymph node involvement while the complete gross resection of the primary tumor mass was feasible. The patient is tumor free after three years of follow-up. Our second patient (age: 5 months) was MYCN negative, INSS Stage 2 and INRGSS Stage 1, as both the primary tumor and the ipsilateral lymph nodes were totally removed via a modified radical neck dissection. The patient is tumor free after three years of follow-up. For MYCN negative patients, especially in early age, the prognosis of neuroblastoma is good, surgical resection and chemotherapy together is an adequate treatment protocol (as in our two patients). While MYCN-amplified patients require a combined and aggressive treatment with surgery, chemotherapy, radiotherapy, and immunotherapy to be able to obtain a favorable survival rate according to the literature. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  10. Olfactory neuroblastoma

    International Nuclear Information System (INIS)

    Rashid, D.; Ahmed, B.; Malik, S.M.; Khan, M.

    2000-01-01

    Olfactory neuroblastoma/esthesioneuroblastoma in a rare malignant tumour of the olfactory neuroepithelium. This is a report of 5 cases managed over the last 10 years at Combined Military Hospital, Rawalpindi. Age of the patients at presentation ranged from 27 to 70 years. The main symptoms were unilateral nasal obstruction and intermittent epistaxis. The mean duration of symptoms at presentation was 11 months. Two patients were staged as B and 3 as C at presentation. The stage of the disease correlated with the duration of symptoms. All the cases were diagnosed on histopathology. Three were offered combination of surgery and radiotherapy. One patient received only surgical treatment and one patient received radiotherapy and chemotherapy. Combination of surgery and radiotherapy showed best results. (author)

  11. Intrarenal neuroblastoma mimics Wilms' tumor

    International Nuclear Information System (INIS)

    Muniz, Maria T. Cartaxo; Soares, Andrezza B.; Freitas, Elizabete M.; Araujo, Marcela; Pureza, Leda M.M.; Morais, Adriana; Antunes, Consuelo; Salles, Terezinha de J. Marques; Borges, Josenilda C.; Morais, Vera L.L. de; Romualdo Filho, Jose; Magalhaes, Mario H.

    2005-01-01

    This work reports the case history of a child with intrarenal neuroblastoma, initially diagnosed as Wilms' tumor. The patient, a one year and three months old girl, presented a hard abdominal mass on the left flank that extended to the meso gastric region, plus fever and paleness. The ultrasound of the entire abdomen revealed an intrarenal mass. Biopsy with fine needle in many points of the tumor revealed Wilms' tumor. The scarcely of the material, however, made immunohistoquemistry impossible at that moment. Because of the child's severe condition the SIOP protocol was started. As no clinical response was observed, an exploratory laparotomy was indicated with partial resection of the tumor and bone marrow aspiration (MO). The histopathologic study revealed a malignant neoplasia of small cells, poorly differentiated. IHQ was negative for WT-1 and positive for NB-84, synaptofisin, cromogranine. N-myc amplification was observed by molecular biology. The bone marrow aspiration identified metastatic small round cells infiltration. Intrarenal neuroblastoma is a rare entity that clinically and radiographically resembles Wilms' tumor. The objective of this case report is to show the importance of immunohistochemical and molecular analysis in the diagnosis of intrarenal neuroblastoma. (author)

  12. Cell Proliferation in Neuroblastoma

    Science.gov (United States)

    Stafman, Laura L.; Beierle, Elizabeth A.

    2016-01-01

    Neuroblastoma, the most common extracranial solid tumor of childhood, continues to carry a dismal prognosis for children diagnosed with advanced stage or relapsed disease. This review focuses upon factors responsible for cell proliferation in neuroblastoma including transcription factors, kinases, and regulators of the cell cycle. Novel therapeutic strategies directed toward these targets in neuroblastoma are discussed. PMID:26771642

  13. Localisation for industrial development

    CSIR Research Space (South Africa)

    Bhugwandin, Ashley

    2017-10-01

    Full Text Available This presentation focuses on localisation for industrial development, and is presented by Ashley Bhugwandin at The 6th CSIR Conference: Ideas that work for industrial development, 5-6 October 2017, CSIR International Convention Centre, Pretoria...

  14. Olfactory Neuroblastoma: Diagnostic Difficulty

    Directory of Open Access Journals (Sweden)

    Vidya MN,

    2011-01-01

    Full Text Available Olfactory neuroblastoma is an uncommon malignant tumor of sinonasal tract arising from the olfactory neuro epithelium. The olfactory neuroblastomas presenting with divergent histomorphologies like, epithelial appearance of cells, lacking a neuro fibrillary background and absence of rosettes are difficult to diagnose. Such cases require immunohistochemistry to establish the diagnosis. We describe the clinical features, pathological and immunohistochemical findings of grade IV Olfactory neuroblastoma in a 57 year old man

  15. Neuroblastoma: computed tomographic findings

    International Nuclear Information System (INIS)

    Yoon, Choon Sik; Ahn, Chang Su; Kim, Myung Jun; Oh, Ki Keun

    1994-01-01

    To evaluate the characteristic CT findings of neuroblastoma, we studied neuroblastomas. We analysed CT findings of available 25 cases among pathologically proved 51 neuroblastomas from Jan. 1983 to Sept. 1990. The most frequent site of origin is adrenal gland (40%) and the second is retroperitoneum (32%) and the third ismediastinum (16%). Characteristic CT findings are as follows: Calcifications within the tumor is detected in 86% of abdominal neuroblastomas and 50% of mediastinal origin. Hemorrhagic and necrotic changes within the tumor is noted at 86% in the tumor of abdominal origin and 25% in mediastinal neuroblastomas. Contrast enhanced study showed frequently seperated enhanced appearance with/without solid contrast enhancement. Encasements of major great vessels such as aorta and IVC with/without displacement by metastatic lymph nodes or tumor are frequently seen in 90% of abdominal neuroblastomas. Multiple lymphadenopathy are detected in 95% of abdominal neuroblastomas and 25% of mediastinal neuroblastomas. The most common organ or contiguous direct invasion is kidney in 6 cases and the next one is liver but intraspinal canal invasion is also noted in 2 cases. We concluded that diagnosis of neuroblastoma would be easily obtained in masses of pediatric group from recognition of above characteristic findings

  16. Neuroblastoma and MYCN

    Science.gov (United States)

    Huang, Miller; Weiss, William A.

    2013-01-01

    Neuroblastoma, the most common extracranial solid tumor of childhood, is thought to originate from undifferentiated neural crest cells. Amplification of the MYC family member, MYCN, is found in ∼25% of cases and correlates with high-risk disease and poor prognosis. Currently, amplification of MYCN remains the best-characterized genetic marker of risk in neuroblastoma. This article reviews roles for MYCN in neuroblastoma and highlights recent identification of other driver mutations. Strategies to target MYCN at the level of protein stability and transcription are also reviewed. PMID:24086065

  17. Drugs Approved for Neuroblastoma

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for neuroblastoma. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  18. Surgical outcome analysis of paediatric thoracic and cervical neuroblastoma.

    Science.gov (United States)

    Parikh, Dakshesh; Short, Melissa; Eshmawy, Mohamed; Brown, Rachel

    2012-03-01

    To identify factors determining the surgical outcome of primary cervical and thoracic neuroblastoma. Twenty-six children with primary thoracic neuroblastoma presented over the last 14 years were analysed for age, mode of presentation, tumour histopathology, biology and outcome. Primary thoracic neuroblastoma was presented in 16 boys and 10 girls at a median age of 2 years (range 6 weeks-15 years). The International Neuroblastoma Staging System (INSS) classified these as Stage 1 (8), Stage 2 (5), Stage 3 (6) and Stage 4 (7). Computed tomography defined the tumour location at the thoracic inlet (11), cervical (2), cervico-thoracic (3), mid-thorax (9) and thoraco-abdominal (1). Twenty-two children underwent surgery that allowed an adequate exposure and resection. Surgical resection was achieved after initial biopsy and preoperative chemotherapy in 15 children, whereas primary resection was performed in 7 children. Four patients with Stage 4 disease underwent chemotherapy alone after initial biopsy; of which, two died despite chemotherapy. Favourable outcome after surgical resection and long-term survival was seen in 19 (86.4%) of the 22 children. Three had local recurrence (14 to 21 months postoperatively), all with unfavourable histology on initial biopsy. The prognostic factors that determined the outcome were age and INSS stage at presentation. In this series, all patients under 2 years of age are still alive, while mortality was seen in five older children. Thoracic neuroblastoma in children under 2 years of age irrespective of stage and histology of the tumour results in long-term survival.

  19. Left atrial mass 16 years after radiation therapy for mediastinal neuroblastoma

    International Nuclear Information System (INIS)

    Ensing, G.J.; Driscoll, D.J.; Smithson, W.A.

    1987-01-01

    Tumors involving the heart during childhood are rare. However, neuroblastoma, a common pediatric malignancy, has been described to involve the cardiovascular system in 3%-12% of patients dying with this tumor. Rarely is such involvement diagnosed ante mortem and never, to our knowledge, has a benign cardiac tumor been reported to present in childhood after successful eradication of neuroblastoma. We describe the identification and surgical resection of a nodular, hypertrophied, calcified, pedunculated left atrial mass in a 16-year-old boy who was complaining of exercise-associated presyncope and headaches 16 years after irradiation and chemotherapy for mediastinal neuroblastoma

  20. Implications of surgical intervention in the treatment of neuroblastomas. 20-year experience of a single institution

    International Nuclear Information System (INIS)

    Tajiri, Tatsuro; Souzaki, Ryota; Kinoshita, Yoshiaki; Koga, Yuhki; Suminoe, Aiko; Hara, Toshiro; Taguchi, Tomoaki

    2012-01-01

    The implications of surgical intervention for neuroblastomas were assessed in one institution. We analyzed the clinical characteristics and extension of resection in 123 pediatric patients with neuroblastoma diagnosed between 1985 and 2004. The 5-year survival rate of the 82 patients under 12 months of age, 59 of whom were treated with complete resection of the primary tumor, was 97%. The 5-year survival rate of the 41 patients over 12 months of age did not differ significantly according to whether complete (n=19) or incomplete resection (n=22) was performed (46 vs. 38%, respectively). No local recurrence was observed in ten patients over 12 months of age with stage 4 disease who underwent complete resection of the primary tumor; however, four of these ten patients died of metastatic recurrence. Considering that the majority of infantile neuroblastomas in this study had favorable biology, complete resection might be unnecessary for patients under 12 years of age. For advanced neuroblastomas in patients over 12 months of age, the main treatment for metastasis is systemic chemotherapy, although extirpation of the primary tumor without extensive surgery might prevent local recurrence when combined with radiation therapy. (author)

  1. Strain localisation in granular media

    OpenAIRE

    Desrues , Jacques

    1984-01-01

    This study is devoted to strain localisation in Granular materials. Both experimental and theoretical results have been obtained.The first part of the thesis is a review of the methods and theories about rupture in sols mechanics and more generally, in solid mechanics. The classical framework of Shear Band analysis is presented, and the main results available for different classes of materials are discussed.The second part describes an experimental study of strain localisation in sand specime...

  2. Diagnostic approach to localised organising pneumonia--A case report.

    Science.gov (United States)

    Djurić, Mirna; Považan, Djordje; Djurić, Dejan; Eri, Živka; Trudić, Anika

    2015-08-01

    Localised organising pneumonia, radiologically presented with oval or round shadows mimicing lung cancer or metastases, is a major issue in differential diagnosis. A female patient was hospitalized to clarified the etiology of multiple nodular lung lesions. The chest X-ray and the chest computed tomography (CT) revealed bilateral patchy and nodular shadows, and round lung lesions, respectively. Neither sputum analyses, nor histology of bronchoscopy samples clarified the etiology of these lung lesions. As secondary deposits in the lungs were suspected, video-assisted thoracoscopy and anterolateral right minithoracotomy with atypical upper and lower lobe resection were performed. The frozen-section analysis suggested the benign nature of the lesion, and the definite histopathological finding of localised organising pneumonia was established. Due to bilateral lung lesions, corticosteroids were applied. Seven weeks later, the chest CT finding revealed a total regression of the lesions. A surgical resection was necessary to diagnose the localised organising pneumonia which mimiced secondary malignant lesions, thus establishing the definite etiology of lung lesions. Bronchoscopic cryobiopsy, recently introduced in order to obtain peripheral lung biopsy samples, has provided new possibilities in the diagnosis and treatment of neoplastic and non-neoplastic lung diseases.

  3. Ureteric angioplasty balloon placement to increase localised dosage of BCG for renal pelvis TCC.

    LENUS (Irish Health Repository)

    Forde, J C

    2012-03-01

    Endoscopic percutaneous resection of a renal pelvis transitional cell carcinoma (TCC) is a viable treatment option in those who would be rendered dialysis dependent following a nephroureterectomy. We report endoscopic percutaneous resection of an upper tract TCC recurrence in a single functioning kidney followed by antegrade renal pelvis BCG instillation with novel placement of inflated angioplasty balloon in the ureter to help localise its effect.

  4. Radiosensitivity of neuroblastoma

    International Nuclear Information System (INIS)

    Deacon, J.M.; Wilson, P.; Steel, G.G.

    1985-01-01

    Neuroblastoma is known to be clinically radioresponsive: it is possible to obtain local tumour control with relatively small doses of radiation. The main therapeutic problem, however, is one of metastatic disease, where in spite of modern combination chemotherapy, the prognosis remains poor. Systemic therapy with either drugs or radiation is dose-limited by toxicity to bone marrow stem cells. However, the advent of new technology which enables tumour cells to be removed from infiltrated marrow prior to autologous bone marrow ''rescue'' allows dose escalation, and makes the use of systemic irradiation in the treatment of stage IV disease feasible. The objective of this study was to investigate the radiobiology of neuroblastoma in detail, including intrinsic cellular radiosensitivity, repair capacity, and extrinsic dose-modifying factors which may affect tumour response in vivo. Cells at three levels of organisation were used: single cell suspensions multicellular tumour spheroids; and xenografts grown in immune-suppressed mice

  5. Mechanisms of neuroblastoma regression

    Science.gov (United States)

    Brodeur, Garrett M.; Bagatell, Rochelle

    2014-01-01

    Recent genomic and biological studies of neuroblastoma have shed light on the dramatic heterogeneity in the clinical behaviour of this disease, which spans from spontaneous regression or differentiation in some patients, to relentless disease progression in others, despite intensive multimodality therapy. This evidence also suggests several possible mechanisms to explain the phenomena of spontaneous regression in neuroblastomas, including neurotrophin deprivation, humoral or cellular immunity, loss of telomerase activity and alterations in epigenetic regulation. A better understanding of the mechanisms of spontaneous regression might help to identify optimal therapeutic approaches for patients with these tumours. Currently, the most druggable mechanism is the delayed activation of developmentally programmed cell death regulated by the tropomyosin receptor kinase A pathway. Indeed, targeted therapy aimed at inhibiting neurotrophin receptors might be used in lieu of conventional chemotherapy or radiation in infants with biologically favourable tumours that require treatment. Alternative approaches consist of breaking immune tolerance to tumour antigens or activating neurotrophin receptor pathways to induce neuronal differentiation. These approaches are likely to be most effective against biologically favourable tumours, but they might also provide insights into treatment of biologically unfavourable tumours. We describe the different mechanisms of spontaneous neuroblastoma regression and the consequent therapeutic approaches. PMID:25331179

  6. Management and outcome of stage 3 neuroblastoma

    Science.gov (United States)

    Modak, Shakeel; Kushner, Brian H.; LaQuaglia, Michael P.; Kramer, Kim; Cheung, Nai-Kong V.

    2013-01-01

    Purpose The management of patients with International Neuroblastoma Staging System (INSS) stage 3 neuroblastoma (NB) is not consistent worldwide. We describe a single centre approach at Memorial Sloan-Kettering Cancer Centre (MSKCC) from 1991 to 2007 that minimizes therapy except for those patients with MYCN-amplified NB. Methods In this retrospective analysis of 69 patients, tumour MYCN was not amplified in 53 and amplified in 16. Event-free survival (EFS) and overall survival (OS) were determined by Kaplan–Meier analysis. Results Fourteen patients with non-MYCN-amplified tumours were treated with surgery alone (group A) and the remaining 39 (group B) with surgery following chemotherapy that was initiated and administered at non-MSKCC institutions. Chemotherapy was discontinued after surgery in 38/39 of the latter. The 10-year EFS and OS for all patients with MYCN-non-amplified NB were 74.9 ± 16.9% and 92.6 ± 5.5%, respectively. There was no difference in OS between groups A and B (p = 0.2; 10-year OS for groups A and B was 84.6 ± 14% and 97.1 ± 2.9%, respectively). Patients with MYCN-amplified disease (group C) underwent dose-intensive induction, tumour resection and local radiotherapy: 13 achieved complete or very good partial remission, and 10 received myeloablative chemotherapy. 11/16 patients also received 3F8-based immunotherapy: 10 remain free of disease. The 10-year EFS and OS for patients with MYCN-amplified neuroblastoma treated with immunotherapy were both 90.9 ± 8.7%. Conclusion Patients with MYCN-non-amplified stage 3 NB can be successfully treated with surgery without the need for radiotherapy or continuation of chemotherapy. Combination of dose-intensive chemotherapy, surgery, radiotherapy and immunotherapy was associated with a favourable outcome for most patients with MYCN-amplified stage 3 NB. PMID:18996003

  7. Image changes of the cases with neuroblastoma observed without therapy

    International Nuclear Information System (INIS)

    Takeuchi, Maho; Aida, Noriko

    1999-01-01

    Fifteen cases (10 males and 5 females) of neuroblastoma diagnosed by mass screening from November 1993 to October 1997, were observed without therapy. The mean age was 7.9 months. There were tumors in para-aortic area in 4 cases, in adrenal parts in 7 cases, in mediastinum in 3 cases. The other case had tumors in mediastinum and adrenal parts, bilaterally. The observation was executed by the ultrasonography in cases with the abdominal tumor and by MRI in cases with the mediastinal tumor. CT, MRI and US were performed in the first examination by radiologist. MIBG scintigraphy was used mainly for the detection of distant metastases. Imaging was performed at every one or two months in the beginning of observation, and at every three or four months afterwards. Tumors reduced in 9 cases, unchanged in 1 case and increased in 5 cases (8 tumors). The change of tumor size could be evaluated accurately, but the prediction of benignity or malignancy was difficult. Pathological findings were obtained from 5 cases who underwent surgical resection. Four cases had increased tumor. Two of them had benign neuroblastoma or ganglioma, and 2 cases had malignant neuroblastoma of low differentiation. One case with decreased tumor had neuroblastoma and became benign. (K.H.)

  8. Neuroblastoma: biology, prognosis, and treatment

    NARCIS (Netherlands)

    Park, Julie R.; Eggert, Angelika; Caron, Huib

    2010-01-01

    Neuroblastoma, a neoplasm of the sympathetic nervous system, is the second most common extracranial malignant tumor of childhood and the most common solid tumor of infancy. Neuroblastoma is a heterogeneous malignancy with prognosis ranging from near uniform survival to high risk for fatal demise.

  9. Neuroblastoma: biology, prognosis, and treatment

    NARCIS (Netherlands)

    Park, Julie R.; Eggert, Angelika; Caron, Huib

    2008-01-01

    Neuroblastoma, a neoplasm of the sympathetic nervous system, is the second most common extracranial malignant tumor of childhood and the most common solid tumor of infancy. Neuroblastoma is a heterogeneous malignancy with prognosis ranging from near uniform survival to high risk for fatal demise.

  10. Neuroblastoma | Office of Cancer Genomics

    Science.gov (United States)

    The TARGET Neuroblastoma projects elucidate comprehensive molecular characterization to determine the genetic changes that drive the initiation and progression of high-risk or hard-to-treat childhood cancers. Neuroblastoma (NBL) is a cancer that arises in immature nerve cells of the sympathetic nervous system, primarily affecting infants and children.

  11. MEIS homeobox genes in neuroblastoma

    NARCIS (Netherlands)

    Geerts, Dirk; Revet, Ingrid; Jorritsma, Gerda; Schilderink, Nathalie; Versteeg, Rogier

    2005-01-01

    The common pediatric tumor neuroblastoma originates from primitive neural crest-derived precursor cells of the peripheral nervous system. Neuroblastoma especially affects very young children, and can already be present at birth. Its early onset and cellular origin predict the involvement of

  12. Colonoscopy and computerised tomography scan are not sufficient to localise right sided colonic lesions accurately.

    LENUS (Irish Health Repository)

    Solon, Jacqueline Gemma

    2009-11-23

    : Aim: accurate pre-operative localisation of colonic lesions is critical especially in laparoscopic colectomy where tactile localisation is absent particularly in screen-detected tumours. The study aimed to evaluate the accuracy of colonoscopy and double-contrast computerised tomography (CT) to localise lesions treated by right hemicolectomy. Method: a retrospective chart review was performed of patients treated by right hemicolectomy under the colorectal service between July 2003 and October 2006. Pre-operative tumour location determined by CT scan and colonoscopy were compared with the intra-operative and histopathologic findings. Results: of 101 patients, 73 (73%) were for adenoma or cancer, with a final diagnosis of adenocarcinoma in 59 (59%). Pre-operative localisation was inaccurate in 29% of lesions using both CT and colonoscopy. In the transverse colon colonoscopy alone was only 37.5% accurate, increasing to 62.5% when information from the CT scan was added. Conclusion: pre-operative localisation of right-sided colon cancers using colonoscopy and CT scanning is unreliable in at least 29% of cases. Inaccurate localisation of transverse colon tumours risks inadequate lymphadenectomy with an adverse cancer outcome. Pre-operative abdominal CT scan improves accuracy but endoscopic tattoo localisation should be employed routinely especially in patients undergoing laparoscopic resection.

  13. Rare localisations of osteochondrosis juvenilis

    Energy Technology Data Exchange (ETDEWEB)

    Schumacher, R; Schuster, W; Mueller, U

    1981-04-01

    A survey of rare localisations of osteochondrosis juvenilis is given and illustrated by cases of Morbus Friedrich, Morbus Panner, Vertebra plana Calve, Morbus Blount, Morbus Iselin, Morbus Hegemann and Morbus Thiemann. This is followed by discussion of etiology and differential diagnosis.

  14. Cystic neuroblastoma: a case report

    International Nuclear Information System (INIS)

    Duran, A.; Lorente, M.L.; Fernandez, C.

    1997-01-01

    Neuroblastoma is the most common neonatal malignant tumor. Hemorrhage and necrosis are usual features of this lesion, but it rarely presents a totally cyst form. We report a case of cystic neuroblastoma detected on prenatal ultrasound and stress the need to include it in the differential diagnosis of cystic abdominal masses in the newborn. Ultrasound is the method of choice for assessing abdominal masses in children. However, magnetic resonance has been shown to be more advantageous for the study and follow-up of neuroblastomas. (Author) 16 refs

  15. Comparing oncologic outcomes after minimally invasive and open surgery for pediatric neuroblastoma and Wilms tumor.

    Science.gov (United States)

    Ezekian, Brian; Englum, Brian R; Gulack, Brian C; Rialon, Kristy L; Kim, Jina; Talbot, Lindsay J; Adibe, Obinna O; Routh, Jonathan C; Tracy, Elisabeth T; Rice, Henry E

    2018-01-01

    Minimally invasive surgery (MIS) has been widely adopted for common operations in pediatric surgery; however, its role in childhood tumors is limited by concerns about oncologic outcomes. We compared open and MIS approaches for pediatric neuroblastoma and Wilms tumor (WT) using a national database. The National Cancer Data Base from 2010 to 2012 was queried for cases of neuroblastoma and WT in children ≤21 years old. Children were classified as receiving open or MIS surgery for definitive resection, with clinical outcomes compared using a propensity matching methodology (two open:one MIS). For children with neuroblastoma, 17% (98 of 579) underwent MIS, while only 5% of children with WT (35 of 695) had an MIS approach for tumor resection. After propensity matching, there was no difference between open and MIS surgery for either tumor for 30-day mortality, readmissions, surgical margin status, and 1- and 3-year survival. However, in both tumors, open surgery more often evaluated lymph nodes and had larger lymph node harvest. Our retrospective review suggests that the use of MIS appears to be a safe method of oncologic resection for select children with neuroblastoma and WT. Further research should clarify which children are the optimal candidates for this approach. © 2017 Wiley Periodicals, Inc.

  16. Cell Survival Signaling in Neuroblastoma

    Science.gov (United States)

    Megison, Michael L.; Gillory, Lauren A.; Beierle, Elizabeth A.

    2013-01-01

    Neuroblastoma is the most common extracranial solid tumor of childhood and is responsible for over 15% of pediatric cancer deaths. Neuroblastoma tumorigenesis and malignant transformation is driven by overexpression and dominance of cell survival pathways and a lack of normal cellular senescence or apoptosis. Therefore, manipulation of cell survival pathways may decrease the malignant potential of these tumors and provide avenues for the development of novel therapeutics. This review focuses on several facets of cell survival pathways including protein kinases (PI3K, AKT, ALK, and FAK), transcription factors (NF-κB, MYCN and p53), and growth factors (IGF, EGF, PDGF, and VEGF). Modulation of each of these factors decreases the growth or otherwise hinders the malignant potential of neuroblastoma, and many therapeutics targeting these pathways are already in the clinical trial phase of development. Continued research and discovery of effective modulators of these pathways will revolutionize the treatment of neuroblastoma. PMID:22934706

  17. Adolescent Neuroblastoma of Lower Limb

    Directory of Open Access Journals (Sweden)

    Rajeshwari K

    2013-04-01

    Full Text Available Neuroblastoma is an embryonic tumour of neural crest origin, commonly seen in children with upper abdomen involvement. Rarely neuroblastomas present in adolescents and adults involving lower limb. Histopathologically neuroblastoma of lower limb can be confused with other small round cell tumour especially with Ewing's sarcoma and rhabdomyosarcoma. A 16 year old male presented with 15x11cm swelling, pain and multiple discharging sinuses of right leg since 4 months. Routine haematological and biochemical analysis were within normal limits. Radiology of right leg showed large soft tissue swelling encompassing the pathological fracture of tibia and bowing of fibula. Fine needle aspiration of the swelling revealed malignant small round cell tumour. Histopathology revealed poorly differentiated neuroblastoma of lower limb. The immunohistochemistry of Synaptophysin and Chromogranin were positive and CD 99 was negative. Neuroblastoma diagnosed at unusual site with uncommon age has poor prognosis. Hence, one must keep in mind the differential diagnosis of neuroblastoma as one of the differential diagnosis in evaluating the soft tissue tumours of lower limb.

  18. Neuroblastoma in Children: Just Diagnosed Information

    Science.gov (United States)

    ... Financial Reports Watchdog Ratings Feedback Contact Select Page Neuroblastoma in Children – Just Diagnosed Home > Cancer Resources > Types ... Diagnosed Just Diagnosed In Treatment After Treatment Diagnosing Neuroblastoma Depending on the location of the tumor and ...

  19. A primary sellar neuroblastoma mimicking a pituitary adenoma: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Dong Gun; Heo, Young Jin; Kim, Eun Kyoung; Baek, Jin Wook; Jeong, Hae Woong; Jung, Hyun Seok [Busan Paik Hospital, Inje University College of Medicine, Busan (Korea, Republic of)

    2016-12-15

    Intracranial neuroblastomas are uncommon malignant tumors that usually arise in the supratentorial parenchymal or paraventricular location. A primary neuroblastoma arising in the sella turcica is extremely rare. We report a case of a 76-year-old man who presented with progressive bitemporal hemianopsia. His pituitary hormone levels were within the normal range, except for slightly increased prolactin. Pituitary magnetic resonance imaging revealed a solitary sellar mass with supra- and parasellar extension that mimicked a non-functioning pituitary adenoma or meningioma. The tumor was excised by transsphenoidal resection. Histopathologic analysis revealed small cells surrounded by a dense fibrillary stroma as well as strong expression of neural markers. Hence, the patient was diagnosed with sellar neuroblastoma. Prolactin levels normalized in the immediate postoperative period, although visual disturbances persisted. Herein, we describe the clinical manifestations, MRI characteristics, and histopathologic findings of this case.

  20. Comparison of DNA aneuploidy, chromosome 1 abnormalities, MYCN amplification and CD44 expression as prognostic factors in neuroblastoma.

    Science.gov (United States)

    Christiansen, H; Sahin, K; Berthold, F; Hero, B; Terpe, H J; Lampert, F

    1995-01-01

    A comparison of the prognostic impact of five molecular variables in a large series was made, including tests of their nonrandom association and multivariate analysis. Molecular data were available for 377 patients and MYCN amplification, cytogenetic chromosome 1p deletion, loss of chromosome 1p heterozygosity, DNA ploidy and CD44 expression were investigated. Their interdependence and influence on event-free survival was tested uni- and multivariately using Pearson's chi 2-test, Kaplan-Meier estimates, log rank tests and the Cox's regression model. MYCN amplification was present in 18% (58/322) of cases and predicted poorer prognosis in localised (P < 0.001), metastatic (P = 0.002) and even 4S (P = 0.040) disease. CD44 expression was found in 86% (127/148) of cases, and was a marker for favourable outcome in patients with neuroblastoma stages 1-3 (P = 0.003) and 4 (P = 0.017). Chromosome 1p deletion was cytogenetically detected in 51% (28/55), and indicated reduced event-free survival in localised neuroblastoma (P = 0.020). DNA ploidy and loss of heterozygosity on chromosome 1p were of less prognostic value. Most factors of prognostic significance were associated with each other. By multivariate analysis, MYCN was selected as the only relevant factor. Risk estimation of high discriminating power is, therefore, possible for patients with localised and metastatic neuroblastoma using stage and MYCN.

  1. Neuroblastoma na Criança: Relato de Caso/Neuroblastoma in Children: Case Report

    Directory of Open Access Journals (Sweden)

    Maysa Carla Mendonça Tame

    2013-03-01

    biological characteristic feature. The clinical presentation is extremely variable, reflecting the possible locations of the primary tumor within the sympathetic nervous system. The most common symptoms include abdominal pain and distention, localized bone pain, systemic symptoms (anorexia, malaise, fever, diarrhea. Is a rare tumor, with an incidence of 10 cases per million children between zero and four years old. Case Report: We report the case of a patient, now four years and eight months, with Neuroblastoma, primary adrenal tumor left adrenal, metastatic to bone marrow bilateral and multiple bones, which started neoadjuvant chemotherapy, immediately after diagnosis, with further evaluation for surgery, adjuvant chemotherapy and radiotherapy, and autologous bone marrow. The treatment is based on stratification of risk group and may involve: chemotherapy, radiation, surgery to remove the tumor and autologous bone marrow. The prognosis is related to the child's age at diagnosis, certain histologic features, staging and tumor genetic alterations. Discussion: Following the protocol, the tumor was staged at level 4, according to the International Neuroblastoma Staging System (INSS and proposed a treatment with multimodality, including an intensive chemotherapy with a combination of agents, followed by surgical resection, high doses of chemotherapy and radiotherapy for subsequent autologous bone marrow transplantation. This treatment was initiated by the patient on 24/08/2011, and is scheduled for a duration of at least one year.

  2. Outcome of children older than one year with neuroblastoma.

    Science.gov (United States)

    Fayea, Najwa Y; Atra, Ayad A; Khattab, Taha; Elimam, Najla A; Felimban, Sami; Yousef, Abdelmoutaleb; Basheer, Ahmed; Zayed, Abdullah; Baothman, Abdullah; Al-Sheikh, Nada; Hussen, Wafa

    2008-01-01

    To assess the outcome of children older than one year with neuroblastoma treated at King Abdul-Aziz Medical City, Jeddah, Kingdom of Saudi Arabia. We retrospectively reviewed the files of 52 children older than one year with neuroblastoma (NBL) treated at our center between September 1987 and May 2003. Treatment consisted of OPEC chemotherapy regimen (vincristine, cisplatin, etoposide, and cyclophosphamide) or alternating OPEC/OJEC (carboplatin in place of cisplatin), surgical resection +/- radiotherapy (RT). No patient received high dose therapy (HDT). Thirty-four patients (65%) were stage 4, 12 (23%) stage 3, and 6 (11%) stage 2. Three stage 2 patients were treated with surgery only, all are alive in complete remission (CR). All stage 3 and 4 patients were treated with chemotherapy and surgery +/- RT. After induction chemotherapy, CR was achieved in 17 patients (32%) and partial remission in 10 (19%). Complete surgical resection was possible in 11 patients (22%). Disease recurrence or progression occurred in 27 patients (51%). With a median follow-up of 24 months (range 4-120), the 2-year event free survival was 10%, 82%, and 87% and the overall survival was 12%, 83%, and 100% for stage 4, 3, and 2. Children older than one year with localized NBL have good prognosis compared to those with stage 4. The use of HDT may improve the outcome in the latter group. Toxicity was significant, and adoption of risk-stratified treatment may help to reduce treatment complications.

  3. Multimodal Localisation: Analysis, Algorithms and Experimental Evaluation

    NARCIS (Netherlands)

    Kavitha Muthukrishnan, K.

    2009-01-01

    The term localisation is derived from the word locale, which traditionally means a small area or vicinity. In ancient days, localisation meant navigation -- an art of finding the way from one place to another. Tremendous advancement in the science of navigation dates back to the sixteenth century,

  4. Quantum localisation on the circle

    Science.gov (United States)

    Fresneda, Rodrigo; Gazeau, Jean Pierre; Noguera, Diego

    2018-05-01

    Covariant integral quantisation using coherent states for semi-direct product groups is implemented for the motion of a particle on the circle. In this case, the phase space is the cylinder, which is viewed as a left coset of the Euclidean group E(2). Coherent states issued from fiducial vectors are labeled by points in the cylinder and depend also on extra parameters. We carry out the corresponding quantisations of the basic classical observables, particularly the angular momentum and the 2π-periodic discontinuous angle function. We compute their corresponding lower symbols. The quantum localisation on the circle is examined through the properties of the angle operator yielded by our procedure, its spectrum and lower symbol, its commutator with the quantum angular momentum, and the resulting Heisenberg inequality. Comparison with other approaches to the long-standing question of the quantum angle is discussed.

  5. Role of surgery in delayed local treatment for INSS 4 neuroblastoma.

    Science.gov (United States)

    Uehara, Shuichiro; Yoneda, Akihiro; Oue, Takaharu; Nakahata, Kengo; Zenitani, Masahiro; Miyamura, Takako; Hashii, Yoshiko; Fukuzawa, Masahiro; Okuyama, Hiroomi

    2017-09-01

    The aim of the present study was to compare the efficacy, complications and outcomes of the following two surgical strategies for delayed local treatment for International Neuroblastoma Staging System (INSS) 4 neuroblastoma (NB): complete resection (CR; period A); and gross total resection/subtotal resection (GTR/STR) with local irradiation (period B). We retrospectively analyzed 17 patients with INSS 4 NB who received delayed local treatment (period A, n = 11; period B, n = 6). Eleven patients in period A received CR. Two patients underwent GTR and four patients underwent STR in period B. The amount of blood loss in period A was significantly greater than that in period B. Postoperative complications were observed in eight patients in period A (73%), but in only one patient in period B (17%; P < 0.01). Recurrence was observed in five patients in period A and in one patient in period B (45.4% vs 16.6%; P = n.s.). Distant metastasis at recurrence was observed in four patients in period A and in one patient in period B. Gross total resection/subtotal resection with local irradiation may be a safe and effective delayed local treatment for INSS 4 NB. © 2017 Japan Pediatric Society.

  6. Nuclear medicine therapy of neuroblastoma

    International Nuclear Information System (INIS)

    Hoefnagel, C.A.

    1999-01-01

    Specific targeting of radionuclides to neuroblastoma, a neural crest tumor occurring predominantly in young children and associated with a relatively poor prognosis, may be achieved via the metabolic route (Mibg), receptor binding (peptides) or immunological approach (antibodies). The clinical role of 1 31 I -Mibg therapy and radioimmunotherapy in neuroblastoma is discussed. In recurrent or progressive metastatic disease after conventional treatment modalities have failed, 1 31 I -Mibg therapy, with an overall objective response rate of 35%, is probably the best palliative treatment, as the invasiveness and toxicity of this therapy compare favourably with that of chemotherapy, immunotherapy and external beam radiotherapy. In patients presenting with inoperable stage III and IV neuroblastoma, 1 31 I -Mibg therapy at diagnosis is at least as effective as combination chemotherapy but is associated with much less toxicity. In patients with recurrent disease 1 31 I -Mibg therapy in combination with hyperbaric oxygen therapy proved feasible and encouraging effects on survival have ben observed. Attempts to intensify the treatment in relapsed patients by combination of 1 31 I -Mibg therapy with high dose chemotherapy and/or total body irradiation have met with considerable toxicity. Developments in Mibg therapy aiming at improving the therapeutic index are mentioned. Early results of radioimmunotherapy using 1 31 I -UJ13A or 1 31 I -3F8 monoclonal antibodies have shown moderate objective response and considerable side effects in patients with stage IV neuroblastoma, who had relapsed or failed conventional therapy. New developments in radioimmunotherapy of neuroblastoma include the use of chimeric antibodies, the enhancement of tumor uptake by modulation of antigen expression or by increasing the tumor perfusion/vascularity/permeability, the use of other labels and multistep targeting techniques, e.g. using bispecific monoclonal antibodies

  7. Prostate resection - minimally invasive

    Science.gov (United States)

    ... thermotherapy; TUMT; Urolift; BPH - resection; Benign prostatic hyperplasia (hypertrophy) - resection; Prostate - enlarged - resection ... passing an instrument through the opening in your penis (meatus). You will be given general anesthesia (asleep ...

  8. Experiences with a new breast localisation needle

    International Nuclear Information System (INIS)

    Hergan, K.; Amann, T.; Doringer, W.; Hollenstein, P.

    1990-01-01

    In view of the increasing number of biopsies of non-palpable lesions of the female breast we found an ideal localisation system in the Hawkins breast localisation needle. Localisation was successful without technical problems in 31 out of 34 patients. The special advantages of the needle are its stability in position and excellent manoeverability due to the construction of the needle. The very simple handling of the needle is an advantage not only for the radiologist but also for the surgeon. (orig.) [de

  9. Advances In Neuroblastoma Diagnostics And Treatment

    International Nuclear Information System (INIS)

    Mazanek, P.; Bajciova, V.; Sterba, J.; Kuglik, P.; Veselsky, R.

    2008-01-01

    Neuroblastoma is the most common extracranial solid tumor of a childhood. Neuroblastoma is well known for its variability in clinical behavioral and distinct biological features. In a history of pediatric oncology it is a first disease, where the biological marker (NMYC amplification) was used for a prospective therapeutical randomisation. Current research is focused on detection of a new biological prognostic markers in neuroblastoma and implementation of a new therapeutical approaches into a clinical practise (eg. antiangiogenic therapies, metronomic chemotherapy, biotherapy, immunotherapy. (author)

  10. Implementing localisation programmes in South Africa

    CSIR Research Space (South Africa)

    Strachan, Garth

    2017-10-01

    Full Text Available challenges – from job creation and poverty reduction to participating in the technological revolution and global value chains, from promoting efficient and clean energy to mitigating climate change and greening the economy – without using some kind... sector value chains where the public sector supports supplier development – e.g. automotives, retail, clothing and textiles etc. Support for technology localisation and diffusion – The Technology Localisation and Implementation Unit [TLIU...

  11. [Resection margins in conservative breast cancer surgery].

    Science.gov (United States)

    Medina Fernández, Francisco Javier; Ayllón Terán, María Dolores; Lombardo Galera, María Sagrario; Rioja Torres, Pilar; Bascuñana Estudillo, Guillermo; Rufián Peña, Sebastián

    2013-01-01

    Conservative breast cancer surgery is facing a new problem: the potential tumour involvement of resection margins. This eventuality has been closely and negatively associated with disease-free survival. Various factors may influence the likelihood of margins being affected, mostly related to the characteristics of the tumour, patient or surgical technique. In the last decade, many studies have attempted to find predictive factors for margin involvement. However, it is currently the new techniques used in the study of margins and tumour localisation that are significantly reducing reoperations in conservative breast cancer surgery. Copyright © 2012 AEC. Published by Elsevier Espana. All rights reserved.

  12. [Cervical neuroblastoma in an infant].

    Science.gov (United States)

    Arvai, Krisztina; Tóth, Judit; Németh, Tamás; Kiss, Csongor; Molnár, Péter; Oláh, Eva

    2004-01-01

    The case of a one-month-old patient admitted to the Department of Pediatrics (Medical and Health Science Center, Debrecen University) because of respiratory distress caused by a cervical mass compressing the upper respiratory pathways is presented. The mass could only be partially removed, the histological diagnosis proved to be neuroblastoma (SBCT: "small blue cell tumor"). Despite the fact that the DNA index of tumor cells (ploidy measurements) and the age of the patient suggested a favourable prognosis, the tumor continued to grow and metastases appeared. Because of symptoms of compression exerted on the respiratory system by the tumor, chemotherapy had to be applied. Since a standard OPEC/OJEC chemotherapeutic protocol proved to be not entirely effective and a residual tumor was still present, retinoic acid and interferon treatment was introduced. Presently, 4 years after the diagnosis, the patient is in complete remission and can be considered to be cured. The case presented here demonstrates that despite the favorable prognosis of the majority of infant neuroblastomas, in some cases the anatomic location of the tumor, leading to disturbance of vital functions, may serve as indication of chemotherapy. Our experience also proved the efficacy of retinoic acid and interferon treatment in relapsed neuroblastoma.

  13. Audit of preoperative localisation of tumor with tattoo for patients undergoing laparoscopic colorectal surgery.

    Science.gov (United States)

    Saleh, A; Ihedioha, U; Babu, B; Evans, J; Kang, P

    2016-08-01

    Preoperative localisation of tumour is an essential requirement in laparoscopic colorectal surgery. Since the introduction of laparoscopic colorectal resections in NGH in February 2010, the difficulties of tumour localisation at the time of surgery without tattoo have been highlighted. Furthermore, endoscopic documentation of site of tattoo with respect to the tumour can be inconsistent and at times misleading or difficult to interpret. Tattooing guidelines should be simple to follow and consistent for all lesions irrespective of the location of the tumour. The recommendations were to place at least three spots of tattoo one mucosal fold distal to the lesion and clearly document site of tattoo with respect to tumour in the endoscopy report. We identified 100 patients undergoing elective laparoscopic colorectal cancer resections over a two-year period. Data were collected regarding presence of tattoo preoperatively as documented in the colonoscopy report and subsequently the visibility of the tattoo at time of laparoscopy and its accuracy in relation to the tumour. Abdominoperineal resections and emergency colorectal operations were excluded. Only 59% of the patients had a visible and accurate tattoo. In 17% of the patients, the tattoo was not visible at all, although it was documented in the endoscopy report that it had been administered. In 4% of patients, it was visible but inaccurately placed. In 20% of the patients, there were no tattoos at all, necessitating on table endoscopy and intraoperative specimen analysis to confirm that the tumour/lesion was within the resection specimen. Preoperative tumour localisation is extremely important to correctly identify the site of tumour or lesion at laparoscopy. A standardised departmental protocol should be implemented by all endoscopists to place three spots of tattoo one mucosal fold distal to any significant lesions found. Failure to tattoo lesions/cancers preoperatively can lead to intraoperative delays and

  14. A Prospective Study of Expectant Observation as Primary Therapy for Neuroblastoma in Young Infants, a Children’s Oncology Group Study

    Science.gov (United States)

    Nuchtern, Jed G.; London, Wendy B.; Barnewolt, Carol E.; Naranjo, Arlene; McGrady, Patrick W.; Geiger, James D.; Diller, Lisa; Schmidt, Mary Lou; Maris, John M.; Cohn, Susan L.; Shamberger, Robert C.

    2015-01-01

    Structured Abstract OBJECTIVE To demonstrate that expectant observation of young infants with small adrenal masses would result in excellent event-free and overall survival (EFS and OS). SUMMARY BACKGROUND DATA Neuroblastoma is the most common malignant tumor in infants, and in young infants, 90% are located in the adrenal gland. Although surgical resection is standard therapy, multiple observations suggest that expectant observation could be a safe alternative for infants 2 were referred for surgical resection. RESULTS 87 eligible patients were enrolled, 83 elected observation and 4 chose immediate surgery. 16 observation patients ultimately had surgery; 8 had INSS stage 1 neuroblastoma, 2 had higher stage neuroblastoma (2B and 4S), 2 had low grade adrenocortical neoplasm, 2 had adrenal hemorrhage and 2 had extralobar pulmonary sequestration. The two patients with adrenocortical tumors were resected because of a >50% increase in tumor volume. The 3-year EFS for a neuroblastoma event was 97.7±2.2% within the entire cohort of patients (n=87). The 3-year overall survival was 100% with median follow-up of 3.2 years. 81% of patients on the observation arm were spared resection. CONCLUSIONS Expectant observation of infants <6 months old with small adrenal masses led to excellent EFS and OS while avoiding surgical intervention in a large majority of the patients. PMID:22964741

  15. Advances in the translational genomics of neuroblastoma

    Science.gov (United States)

    Bosse, Kristopher R.; Maris, John M.

    2015-01-01

    Neuroblastoma is an embryonal malignancy that commonly affects young children and is remarkably heterogenous in its malignant potential. Recently, the genetic basis of neuroblastoma has come into focus, which has catalyzed not only a more comprehensive understanding of neuroblastoma tumorigenesis, but has also revealed novel oncogenic vulnerabilities that are being leveraged therapeutically. Neuroblastoma is a model pediatric solid tumor in its use of recurrent genomic alterations, such as high-level MYCN amplification, for risk stratification. Given the relative paucity of recurrent activating somatic point mutations or gene fusions in primary neuroblastoma tumors studied at initial diagnosis, innovative treatment approaches beyond small molecules targeting mutated or dysregulated kinases will be required moving forward to achieve noticeable improvements in overall patient survival. However, the clonally acquired, oncogenic aberrations in relapsed neuroblastomas are currently being defined and may offer an opportunity to improve patient outcomes with molecularly targeted therapy directed towards aberrantly regulated pathways in relapsed disease. This review will summarize the current state of knowledge of neuroblastoma genetics and genomics, highlighting the improved prognostication and potential therapeutic opportunities that have arisen from recent advances in understanding germline predisposition, recurrent segmental chromosomal alterations, somatic point mutations and translocations, and clonal evolution in relapsed neuroblastoma. PMID:26539795

  16. CT diagnosis of neuroblastoma in childhood

    International Nuclear Information System (INIS)

    Li Xin; Zhang Liqun; Yang Zhiyong

    1997-01-01

    Purpose: To evaluate CT in the diagnosis of neuroblastoma in childhood. Materials and methods: Analysis of CT manifestations in 26 cases proved by operation and pathology, including neuroblastoma 21 cases, ganglioneuroblastoma 5 cases. Thorax 7 cases (27%), adrenal gland 16 cases (62%), abdomen-pelvis paravertebral sympathetic chain 3 cases (11%). Bolus injection of contrast medium was given in all cases. Results: Adrenal gland and posterior superior mediastinum were the most common sites for neuroblastoma. 73% of neuroblastoma had calcifications. Neuroblastoma was more commonly calcified than ganglioneuroblastoma. Metastases were also calcified. Degree of enhancement was associated with the type of neuroblastoma. Tumor extension into the spinal canal was seen in 2 cases. 43% neuroblastoma of adrenal directly invaded the kidney in 7 cases. Right lobe of liver was involved in 3 cases, metastases to liver in 1 case, enlargement of lymph nodes 19 cases. Approximately 68% of patients showed increase of urinary Vanilly-mandelic acid (VMA). Preoperative diagnostic accuracy was 92%. Conclusion: CT is recognized as a useful technique for the diagnosis of neuroblastoma. The site of predilection, calcification, lymph node metastases and VMA increase in urine or serum are important basis for diagnosis

  17. Neuroblastoma : Crossing borders in targeted therapy

    NARCIS (Netherlands)

    Bate-Eya, L.T.

    2017-01-01

    Neuroblastoma is the most commonly diagnosed childhood cancer and accounts for about 15% of all pediatric malignancies deaths. Thus far, the treatment options of neuroblastoma is limited with only a 30-40% long term survival rate in high-risk patients. In this thesis, we describe the isolation and

  18. POSTTREATMENT NEUROBLASTOMA MATURATION TO GANGLIONIC CELL TUMOR

    Directory of Open Access Journals (Sweden)

    M. V. Ryzhova

    2012-01-01

    Full Text Available Tumor cells can differentiate into more mature forms in undifferentiated or poorly differentiated tumors, such as medulloblastomas with increased nodularity, as well as neuroblastomas. The authors describe 2 cases of neuroblastoma maturation into ganglioneuroblastoma 5 months after chemotherapy in a 2-year-old girl and 3 years after radiotherapy in a 16-year-old girl.

  19. Congenital bilateral neuroblastoma (stage IV-S): case report

    International Nuclear Information System (INIS)

    Lee, Jeong Hee; Lee, Hee Jung; Woo, Seong Ku; Lee, Sang Rak; Kim, Heung Sik

    2002-01-01

    Congenital neonatal neuroblastoma is not uncommon but bilateral adrenal neuroblastoma is rare, accounting for about ten percent of neuroblastomas in children. We report the US the MR findings of a stage IV-S congenital bilateral neuroblastoma occurring in a one-day-old neonate

  20. Sublethal irradiation promotes invasiveness of neuroblastoma cells

    International Nuclear Information System (INIS)

    Schweigerer, Lothar; Rave-Fraenk, Margret; Schmidberger, Heinz; Hecht, Monica

    2005-01-01

    Neuroblastoma is the most frequent extracranial solid tumour of childhood. Despite multiple clinical efforts, clinical outcome has remained poor. Neuroblastoma is considered to be radiosensitive, but some clinical studies including the German trial NB90 failed to show a clinical benefit of radiation therapy. The mechanisms underlying this apparent discrepancy are still unclear. We have therefore investigated the effects of radiation on neuroblastoma cell behaviour in vitro. We show that sublethal doses of irradiation up-regulated the expression of the hepatocyte growth factor (HGF) and its receptor c-Met in some neuroblastoma cell lines. The increase in HGF/c-Met expression was correlated with enhanced invasiveness and activation of proteases degrading the extracellular matrix. Thus, irradiation at sublethal doses may promote the metastatic dissemination of neuroblastoma cells through activating the HGF/c-Met pathway and triggering matrix degradation

  1. [Repeat hepatic resections].

    Science.gov (United States)

    Popescu, I; Ciurea, S; Braşoveanu, V; Pietrăreanu, D; Tulbure, D; Georgescu, S; Stănescu, D; Herlea, V

    1998-01-01

    Five cases of iterative liver resections are presented, out of a total of 150 hepatectomies performed between 1.01.1995-1.01.1998. The resections were carried out for recurrent adenoma (one case), cholangiocarcinoma (two cases), hepatocellular carcinoma (one case), colo-rectal cancer metastasis (one case). Only cases with at least one major hepatic resection were included. Re-resections were more difficult than the primary resection due, first of all, to the modified vascular anatomy. Intraoperative ultrasound permitted localization of intrahepatic recurrences. Iterative liver resection appears to be the best therapeutical choice for patients with recurrent liver tumors.

  2. Intestinal Lymphangiectasia Secondary to Neuroblastoma

    Directory of Open Access Journals (Sweden)

    RM Reifen

    1994-01-01

    Full Text Available An eight month-old infant presented with a 10-day history of vomiting and diarrhea, and a one-week history of swelling of the lower extremities. Laboratory evaluations revealed hypoproteinemia and lymphocytopenia due to protein-losing enteropathy. Peroral small bowel biopsy showed intestinal lymphangiectasia. Subsequent onset of unexplained ecchymosis and obstructive jaundice resulted in additional studies which revealed an omental neuroblastoma as the underlying etiology of the infant’s symptoms. This report emphasizes the importance of considering secondary, obstructive causes for lymphangiectasia and protein-losing enteropathy.

  3. MIBG-treatment in neuroblastoma

    International Nuclear Information System (INIS)

    Treuner, J.; Gerein, V.; Klingebiel, T.; Schwabe, D.; Feine, U; Happ, J.; Niethammer, D.; Maul, F.; Dopfer, R.; Kornhuber, B.; Berthold, F.; Jurgens, H.; Hor, G.

    1988-01-01

    This paper reports the results of 27 children with neuroblastoma treated with 131 I-Metaiodobenzylguanidine (MIBG). They were either refractory to conventional therapy or experienced relapse after initially successful treatment. 7 children revealed stage IV and 20 stage III at the beginning of MIBG-treatment. MIBG was administered by infusion lasting from 30 min to 30 hrs. In most children the dose was split into two portions each infused over a period of 4 hrs with a 24 hrs interval between. Courses were repeated up to 6 times and maximum activity given to one patient cumulatively was 38,221 MBq. 24 patients were valuable for analysis of results

  4. Weak Localisation in Clean and Highly Disordered Graphene

    International Nuclear Information System (INIS)

    Hilke, Michael; Massicotte, Mathieu; Whiteway, Eric; Yu, Victor

    2013-01-01

    We look at the magnetic field induced weak localisation peak of graphene samples with different mobilities. At very low temperatures, low mobility samples exhibit a very broad peak as a function of the magnetic field, in contrast to higher mobility samples, where the weak localisation peak is very sharp. We analyze the experimental data in the context of the localisation length, which allows us to extract, both the localisation length and the phase coherence length of the samples, regardless of their mobilities. This analysis is made possible by the observation that the localisation length undergoes a generic weak localisation dependence with striking universal properties

  5. Locoregional Tumor Progression After Radiation Therapy Influences Overall Survival in Pediatric Patients With Neuroblastoma

    International Nuclear Information System (INIS)

    Pai Panandiker, Atmaram S.; McGregor, Lisa; Krasin, Matthew J.; Wu Shengjie; Xiong Xiaoping; Merchant, Thomas E.

    2010-01-01

    Purpose: There is renewed attention to primary site irradiation and local control for patients with high-risk neuroblastoma (NB). We conducted a retrospective review to identify factors that might predict for locoregional tumor control and its impact on overall survival. Methods and Materials: Between July 2000 through August 2006, a total of 44 pediatric patients with NB received radiation therapy (RT) with curative intent using computed tomography (CT)-based treatment planning. The median age was 3.4 years and the median cumulative dose was 23.4 Gy. Overall survival and locoregional tumor control were measured from the start of RT to the date of death or event as determined by CT/magnetic resonance imaging/meta-iodobenzylguanidine. The influence of age at irradiation, gender, race, cumulative radiation dose, International Neuroblastoma Staging System stage, treatment protocol and resection status was determined with respect to locoregional tumor control. Results: With a median follow-up of 34 months ± 21 months, locoregional tumor progression was observed in 11 (25%) and was evenly divided between primary site and adjacent nodal/visceral site failure. The influence of locoregional control reached borderline statistical significance (p = 0.06). Age (p = 0.5), dose (p = 0.6), resection status (p = 0.7), and International Neuroblastoma Staging System stage (p = 0.08) did not influence overall survival. Conclusions: Overall survival in high-risk neuroblastoma is influenced by locoregional tumor control. Despite CT-based planning, progression in adjacent nodal/visceral sites appears to be common; this requires further investigation regarding target volume definitions, dose, and the effects of systemic therapy.

  6. Case report: value of gene expression profiling in the diagnosis of atypical neuroblastoma.

    Science.gov (United States)

    Harttrampf, Anne C; Chen, Qingrong; Jüttner, Eva; Geiger, Julia; Vansant, Gordon; Khan, Javed; Kontny, Udo

    2017-08-17

    Nephroblastoma and neuroblastoma belong to the most common abdominal malignancies in childhood. Similarities in the initial presentation may provide difficulties in distinguishing between these two entities, especially if unusual variations to prevalent patterns of disease manifestation occur. Because of the risk of tumor rupture, European protocols do not require biopsy for diagnosis, which leads to misdiagnosis in some cases. We report on a 4½-year-old girl with a renal tumor displaying radiological and laboratory characteristics supporting the diagnosis of nephroblastoma. Imaging studies showed tumor extension into the inferior vena cava and bilateral lung metastases while urine catecholamines and MIBG-scintigraphy were negative. Preoperative chemotherapy with vincristine, actinomycine D and adriamycin according to the SIOP2001/GPOH protocol for the treatment of nephroblastoma was initiated and followed by surgical tumor resection. Histopathology revealed an undifferentiated tumor with expression of neuronal markers, suggestive of neuroblastoma. MYCN amplification could not be detected. DNA-microarray analysis was performed using Affymetrix genechip human genome U133 plus 2.0 and artificial neural network analysis. Results were confirmed by multiplex RT-PCR. Principal component analysis using 84 genes showed that the patient sample was clearly clustering with neuroblastoma tumors. This was confirmed by hierarchical clustering of the multiplex RT-PCR data. The patient underwent treatment for high-risk neuroblastoma comprising chemotherapy including cisplatin, etoposide, vindesine, dacarbacine, ifosfamide, vincristine, adriamycine and autologous stem cell transplantation followed by maintenance therapy with 13-cis retinoic acid (GPOH NB2004 High Risk Trial Protocol) and is in complete long-term remission. The use of gene expression profiling in an individual patient strongly contributed to clarification in a diagnostic dilemma which finally led to a change of

  7. Image-defined Risk Factors Correlate with Surgical Radicality and Local Recurrence in Patients with Neuroblastoma.

    Science.gov (United States)

    Pohl, A; Erichsen, M; Stehr, M; Hubertus, J; Bergmann, F; Kammer, B; von Schweinitz, D

    2016-04-01

    Neuroblastoma is the second most common solid pediatric tumor and the most common cancer to be detected in children younger than 12 months of age. To date, 2 different staging systems describe the extent of the disease: the International Neuroblastoma Staging System (INSS) and the International Neuroblastoma Risk Group Staging System (INRGSS). The INRGSS-system is characterized by the presence or absence of so called image-defined risk factors (IDRFs), which are described as surgical risk factors. We hypothesized that IDRFs correlate with surgical complications, surgical radicality, local recurrence and overall survival (OS). Between 2003 and 2010, 102 patients had neuroblastoma surgery performed in our department. We analyzed medical records for IDRF-status and above named data. 16 patients were IDRF-negative, whereas 86 patients showed one or more IDRF. Intra- or postoperative complications have been reported in 21 patients (21%). 19 of them showed one or more IDRF and 2 patients were IDRF-negative (p=n.s.). Patients who suffered from intra- or postoperative complications demonstrated a decreased OS (p=0.011). Statistical analysis revealed an inverse correlation between the extent of macroscopical removal and IDRF-status (p=0.001). Furthermore, the number of IDRFs were associated with a decreased likelihood of radical tumor resection (p<0.001). 19 patients had local recurrence; all of them were IDRF-positive (p=0.037). Pediatric surgeons should consider IDRFs as a useful tool for risk assessment and therefore planning for neuroblastoma surgery. © Georg Thieme Verlag KG Stuttgart · New York.

  8. Typical skeletal changes due to metastasising neuroblastomas

    International Nuclear Information System (INIS)

    Eggerath, A.; Persigehl, M.; Mertens, R.; Technische Hochschule Aachen

    1983-01-01

    Compared with other solid tumours in childhood, neuroblastomas show a marked tendency to metastasise to the skeleton. The differentiation of these lesions from inflammatory and other malignant bone lesions in this age group is often difficult. The radiological findings in ten patients with metastasing and histologically confirmed neuroblastomas have been reviewed and the typical appearances in the skeleton are described. The most important features in the differential diagnosies are discussed and the significance of bone changes in the diagnosis of neuroblastoma have been evaluated. (orig.) [de

  9. Mesenteric vein thrombosis after percitaneous transhepatic portal vein catheterisation for the localisation of an insulinoma

    International Nuclear Information System (INIS)

    Luska, G.; Langer, H.E.; Le Blanc, S.; Medizinische Hochschule Hannover

    1984-01-01

    The authors report on a fatal mesenteric vein thrombosis following an uncomplicated percutaneous transhepatic portal vein catheterisation for the localisation of an insulinoma. Several hours after the procedure the patient developed an acute abdomen. An emergency laparotomy revealed a haemorrhagic infarct of the ileum. The resected specimen showed an acute phlebitis with fresh thrombus. The cause of the phlebothrombosis was thought to be intimal damage from high osmolar contrast medium. There was no evidence of damage due to the catheder, either on the phlebogram or pathologically. (orig.) [de

  10. Primary localised cutaneous amyloidosis - a systematic review

    DEFF Research Database (Denmark)

    Kaltoft, Britta; Schmidt, Grethe; Lauritzen, Anne Falensteen

    2013-01-01

    Amyloidosis is defined as extracellular deposits of heterogenic, misfolded proteins, amyloid fibrils, in various tissues. The aim of our study was to review the literature and to evaluate the risk of developing systemic amyloidosis (SA) and the risk of local recurrence of primary localised...

  11. Comparing mobile robot localisation algorithms using Kalmtool

    DEFF Research Database (Denmark)

    Mogensen, Lars Valdemar; Hansen, Søren; Ravn, Ole

    2009-01-01

    In this paper we present an estimation platform with simulation capabilities to evaluate methods for localisation of a mobile robot using a feature map. The platform is based on the Kalmtool 4 toolbox which is a set of MATLAB tools for state estimation of nonlinear systems. The toolbox contains...

  12. Search and localisation of CERN buildings

    CERN Multimedia

    TS/FM - Patrimony and Site Information Section

    2005-01-01

    A new, updated version of the web application allowing search and localisation of CERN buildings has been available since 20 May 2005. You can now find a specific building, road, car-park and other information regarding the CERN sites. For comments or enquiries please contact SIG.Support@cern.ch TS/FM - Patrimony and Site Information Section (ISP)

  13. Neuronal NOS localises to human airway cilia.

    Science.gov (United States)

    Jackson, Claire L; Lucas, Jane S; Walker, Woolf T; Owen, Holly; Premadeva, Irnthu; Lackie, Peter M

    2015-01-30

    Airway NO synthase (NOS) isoenzymes are responsible for rapid and localised nitric oxide (NO) production and are expressed in airway epithelium. We sought to determine the localisation of neuronal NOS (nNOS) in airway epithelium due to the paucity of evidence. Sections of healthy human bronchial tissue in glycol methacrylate resin and human nasal polyps in paraffin wax were immunohistochemically labelled and reproducibly demonstrated nNOS immunoreactivity, particularly at the proximal portion of cilia; this immunoreactivity was blocked by a specific nNOS peptide fragment. Healthy human epithelial cells differentiated at an air-liquid interface (ALI) confirmed the presence of all three NOS isoenzymes by immunofluorescence labelling. Only nNOS immunoreactivity was specific to the ciliary axonemeand co-localised with the cilia marker β-tubulin in the proximal part of the ciliary axoneme. We report a novel localisation of nNOS at the proximal portion of cilia in airway epithelium and conclude that its independent and local regulation of NO levels is crucial for normal cilia function. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Generalised two target localisation using passive monopulse radar

    KAUST Repository

    Jardak, Seifallah; Ahmed, Sajid; Alouini, Mohamed-Slim

    2017-01-01

    The simultaneous lobing technique, also known as monopulse technique, has been widely used for fast target localisation and tracking purposes. Many works focused on accurately localising one or two targets lying within a narrow beam centred around

  15. Neuroblastoma Treatment (PDQ®)—Patient Version

    Science.gov (United States)

    Neuroblastoma treatment may include surgery, observation, chemotherapy, radiation therapy, radioactive iodine, and high-dose chemotherapy with stem cell transplant and targeted therapy. Treatment also depends on risk category. Learn more in this expert-reviewed summary.

  16. Narcolepsy/Cataplexy and Occult Neuroblastoma

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2013-11-01

    Full Text Available Investigators at the University of Chicago and Northwestern University, Chicago, IL; University Hospital Southampton, UK; and Kiev Paediatric Hospital, Ukraine, report three children with narcolepsy and cataplexy subsequently diagnosed with neuroblastoma.

  17. Evidence of chromaffin oxygen sensing in neuroblastoma.

    Science.gov (United States)

    Hedborg, F; Franklin, G; Norrman, J; Grimelius, L; Wassberg, E; Hero, B; Schilling, F; Berthold, F; Harms, D; Sandstedt, B

    2001-01-01

    With the aid of IGF2 and VEGF in situ hybridization; tyrosine hydroxylase, chromogranin A, and Ki67 immunohistochemistry; and TUNEL staining applied to a large series of clinical neuroblastomas and to an animal model, we show here that stroma-poor neuroblastomas show evidence of chromaffin differentiation similar to that of type 1 small intensely fluorescent (SIF) cells and that this occurs in a vascular-dependent fashion, indicating a role for local tumor hypoxia in the differentiation process.

  18. Localised perforation of locally advanced transverse colon cancer with spontaneous colocutaneous fistula formation: a clinical challenge.

    Science.gov (United States)

    Wadhwani, Nikita; Diwakar, Deepak Kumar

    2018-04-19

    Colon cancer can present with complications such as obstruction, perforation and bleeding. The clinical presentation has been recognised as an independent prognostic factor for morbidity and mortality. 1 We present a rare case of localised perforation of a locally advanced colon cancer arising from mid-transverse colon in an elderly woman in the absence of widely metastatic disease with eventual cutaneous involvement of the overlying skin by direct extension, resulting in formation of colocutaneous fistula. The management of such cases is complex as usually tailored to the situation encountered. 2 This case was a clinical challenge to choose between initial palliative resection and curative R0 resection following neoadjuvant chemotherapy. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  19. An epidural neuroblastoma causing spinal cord compression in a 67-year-old woman

    Directory of Open Access Journals (Sweden)

    Ethan Taub

    2010-04-01

    Full Text Available We report a case of disseminated neuroblastoma (NB causing epidural spinal cord compression in a 67-year-old woman. Because NB is primarily a tumor of infancy and childhood, less is known about its clinical course and optimal treatment in adults. This patient was treated with a thoracic laminectomy and tumor resection; polychemotherapy with one cycle of vindesine, cisplatin, and etoposide; one cycle of vincristine, dacarbazine, ifosfamide, and doxorubicin; and radiotherapy to the spine. She remained able to walk but died 8.5 months later of diffuse systemic tumor progression.

  20. Antitumor Effect of Burchellin Derivatives Against Neuroblastoma.

    Science.gov (United States)

    Kurita, Masahiro; Takada, Tomomi; Wakabayashi, Noriko; Asami, Satoru; Ono, Shinichi; Uchiyama, Taketo; Suzuki, Takashi

    2018-02-01

    Neuroblastoma is one of the most commonly encountered malignant solid tumors in the pediatric age group. We examined the antitumor effects of five burchellin derivatives against human neuroblastoma cell lines. We evaluated cytotoxicity by the MTT assay for four human neuroblastoma and two normal cell lines. We also performed analysis of the apoptotic induction effect by flow cytometry, and examined the expression levels of apoptosis- and cell growth-related proteins by western blot analysis. We found that one of the burchellin derivatives (compound 4 ) exerted cytotoxicity against the neuroblastoma cell lines. Compound 4 induced caspase-dependent apoptosis via a mitochondrial pathway. The apoptosis mechanisms induced by compound 4 involved caspase-3, -7 and -9 activation and poly (ADP-ribose) polymerase cleavage. In addition, compound 4 induced cell death through inhibition of the cell growth pathway (via extracellular signal-regulated kinase 1 and 2, AKT8 virus oncogene cellular homolog, and signal transducer and activator of transcription 3). Compound 4 exerted cellular cytotoxicity against neuroblastoma cells via induction of caspase-dependent apoptosis, and may offer promise for further development as a useful drug for the treatment of advanced neuroblastoma. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  1. Olfactory neuroblastoma: a single-center experience.

    Science.gov (United States)

    König, Marton; Osnes, Terje; Jebsen, Peter; Evensen, Jan Folkvard; Meling, Torstein R

    2018-01-01

    Olfactory neuroblastoma (ONB) is a potentially curable disease, despite being an aggressive malignancy with a poor natural history. Our goal was to evaluate management outcomes for patients with ONB treated at our institution. Our prospective database for brain tumors and the pathology registry of head and neck cancers at Oslo University Hospital were searched to identify all patients treated for ONB between 1998 and 2016. Variables extracted from these databases, supplemented by retrospective chart reviews, underwent thorough analysis. All cases were formally re-examined by a dedicated head and neck pathologist. Twenty patients were identified. Follow-up was 100%. Mean follow-up was 81.5 months for the entire cohort and 120.3 months for patients with no evidence of disease. Fourteen patients underwent treatment of choice including craniofacial resection (CFR) with or without radiotherapy (XRT). Six patients could only receive less extensive treatment; three patients underwent lateral rhinotomy (LR) with or without XRT after being deemed medically unsuitable for CFR, while another three patients received only supportive, non-surgical treatment (due to positive lymph node status in two and to extensive tumor size in one case). Overall and disease-specific survival rates were 100% after 10 years of follow-up when negative surgical margins were achieved by CFR. Positive margins were associated with poorer outcome with no patients surviving longer than 44 months. Long-term survival was also achieved in two cases among patients not eligible for CFR: one case after radical LR and one case after radio-chemotherapy. Advanced disease at presentation (tumor size ≥40 mm, Kadish grades C and D, or TNM IVa and IVb) and positive surgical margins were correlated to significantly dismal survival. Our study suggests that CFR with or without adjuvant XRT is safe and leads to excellent long-time overall and disease-specific survival. Negative surgical margins, tumor size <40

  2. Localised Microwave Bursts During ELMs on MAST

    Directory of Open Access Journals (Sweden)

    Freethy Simon

    2015-01-01

    Full Text Available Bursts of microwave emission are observed during ELM events on the Mega Ampère Spherical Tokamak. In agreement with observations on other machines, these bursts are up to 3 orders of magnitude more intense than the thermal background, but are electron cyclotron in nature. The peak in microwave emission is ~20μ before the peak in midplane Dα emission. Using the Synthetic Aperture Microwave Imaging radiometer, we are able to demonstrate that these bursts are often highly spatially localised and preferentially occur at the tokamak midplane. It is hypothesised that the localisation is a result of Doppler resonance broadening for electron Bernstein waves and the high perpendicular electron energies could be the result of pitch angle scattering in high collisionality regions of the plasma.

  3. A Localised Corrosion Cell for Industrial Applications

    DEFF Research Database (Denmark)

    Andersen, A.; Hilbert, Lisbeth Rischel; Jansen, P.

    2003-01-01

    The LOCORR-CELL™ developed by FORCE TECHNOLOGY is an electrochemical cell for industrial applications estimating localised corrosion. The cell is constructed in a carbon steel casing for direct mounting into the system. It is based on an oxygen concentration element reflecting the interaction...... between the environment formed under a deposit or in a crevice. The essential feature of the method is that it reflects the influence of oxygen content, conductivity and temperature as well as the influence of corrosion inhibitors, MIC and other effects that have an effect on localised corrosion under...... deposits and in crevices. The measuring principle in the cell is based on measurements of the galvanic current flow between the steel anode covered by a porous glass frit and the surrounding steel casing. The current is measured by a zero-resistance circuit-instrument and the activity can be presented...

  4. The Role of Localisation in Advertising Translation

    Institute of Scientific and Technical Information of China (English)

    ZHANG Ying

    2016-01-01

    Today, a growing number of international corporations have been seeking to boost their sales on the global scale. To achieve this, adverting, one of the most common way to stimulate consumption, is widely used in which translation is involved because of diverse languages. Thus, how to translate a source advertising in a target culture has a decisive influence on a compa-ny’s marketing. The aim of the target advertising is to sell products to the locals. In this sense, localisation plays a significant role in the translation of advertising. This essay will discuss the importance of localisation in the translation of advertising and analyse cases of English-Chinese advertising translation based on the purpose of advertising and advertising translation.

  5. Problems associated with localised skin exposures

    International Nuclear Information System (INIS)

    Wells, J.

    1986-01-01

    The possible sources of localised skin exposure include small commercial sources (for radiotherapy, for example), radiopharmaceuticals, collimated microbeams, and both fission and activation products from nuclear reactors, neutron generators and associated facilities. Each of these sources has its own particular characteristics and associated problems. Recommendations and regulations relating to limits on skin dose for such exposures have been constrained by inadequate radiobiological data and the limitations inherent in personal dosimetric techniques. A growing body of data is now available for beta-emitters which allows a preliminary reassessment of some aspects of the currently recommended dose limits for localised skin exposures. How the skin dose is measured is particularly important for such exposures, as doses often have to be averaged over a specific area. The area chosen for dose measurement and the depth at which the measurement is made are crucial to understanding the possible biological consequences and for formulating appropriate protection criteria. (author)

  6. Cholinergic regulation of VIP gene expression in human neuroblastoma cells

    DEFF Research Database (Denmark)

    Kristensen, Bo; Georg, Birgitte; Fahrenkrug, Jan

    1997-01-01

    Vasoactive intestinal polypeptide, muscarinic receptor, neuroblastoma cell, mRNA, gene expression, peptide processing......Vasoactive intestinal polypeptide, muscarinic receptor, neuroblastoma cell, mRNA, gene expression, peptide processing...

  7. Neuroblastoma

    Science.gov (United States)

    ... the cancer has spread to the bones or bone marrow) weakness, numbness, inability to move a body part, or difficulty walking (if the cancer presses on the spinal cord) drooping eyelid, unequal pupils, sweating, and red ...

  8. 'Localised creativity: a life span perspective'

    OpenAIRE

    Worth, Piers J.

    2000-01-01

    This thesis is based around a biographic study of the lives of 40 individuals (24 men and 16 women) with a reputation for creative work in a localised context (such as an organisation). The study examines life span development patterns from birth to middle age (45 - 60 years of age) with data gained by biographic interview and thematic analysis. Participants selected for this study are creative in that they have a reputation for producing new, novel and useful or appropriate contributions in ...

  9. Metastatic neuroblastoma in the brain parenchyma; a case report

    International Nuclear Information System (INIS)

    Kim, Ho Sung; Choi, Choong Gon; Shin, Ji Hoon; Lee, Ho Kyu; Suh, Dae Chul

    2000-01-01

    During childhood, neuroblastoma is a relatively common malignant neoplasm which commonly metastasizes to other organs. Metastasis to the central nervous system from an extracranial neuroblastoma is rare, however, and brain parenchymal metastasis is very rare. We describe a case of brain parenchymal metastasis from primary abdominal neuroblastoma, and review the literature

  10. Hyperfractionated radiotherapy (2100 cGY) for stage 4 neuroblastoma as part of intensive multimodality therapy

    International Nuclear Information System (INIS)

    Gollamudi, S.V.; Kushner, B.H.; Merchant, T.E.; LaQuaglia, M.; Lindsley, K.; Rosenfield, N.; Abramson, S.; Kramer, K.; Cheung, N.K.V.

    1997-01-01

    PURPOSE: To retrospectively evaluate the role of hyperfractionated radiotherapy to the primary site following induction chemotherapy and aggressive surgical resection in patients (pts) with stage 4 neuroblastoma. MATERIALS AND METHODS: 48 previously untreated children (median age at diagnosis 3 yo, range 1-10 yo) with stage 4 neuroblastoma achieved a complete-, near-complete-, or partial-remission after multimodality therapy (protocol N4: 6 pts, N5: 7 pts, N6: 27 pts, or N7: 8 pts). All protocols included a regimen consisting of dose-intensive multiagent chemotherapy, maximal surgical debulking, followed by hyperfractionated radiotherapy. Most pts then underwent consolidation with either autologous marrow transplantation (N4 and N5), or immunotherapy (N6 and N7) with radioimmunotherapy (N7). Of 48 pts, 46 had microscopic disease at the primary site prior to beginning radiotherapy (45 underwent gross total resection of the primary, and one had no residual primary disease after chemotherapy alone). One pt had a partial resection, and one remained unresectable after mutimodality therapy. The pre-chemotherapy volume of the primary tumor and regional lymph nodes were irradiated to a total dose of 2100cGy delivered twice-daily in 150 cGy fractions over 7 treatment days. RESULTS: With a median follow-up of 32.5 months (range= 8-145 months), local-regional control was achieved in 44 of the 48 pts. Of the pts who are progression-free, median follow-up was 53.5 months. Overall, 24 of 48 pts progressed, three with local-regional recurrence as the first site of relapse, one with distant failure first and subsequent local-regional recurrence, and 21 with distant failure only. The probability of local-regional control at 32 months was 83%. One of the four pts with local-regional relapse never achieved a complete remission with either systemic therapy, surgical resection or radiotherapy. The progression-free survival at 32 months was 46%. Median time to overall progression was 16

  11. Excessive blinking and ataxia in a child with occult neuroblastoma and voltage-gated potassium channel antibodies.

    LENUS (Irish Health Repository)

    Allen, Nicholas M

    2012-05-01

    A previously healthy 9-year-old girl presented with a 10-day history of slowly progressive unsteadiness, slurred speech, and behavior change. On examination there was cerebellar ataxia and dysarthria, excessive blinking, subtle perioral myoclonus, and labile mood. The finding of oligoclonal bands in the cerebrospinal fluid prompted paraneoplastic serological evaluation and search for an occult neural crest tumor. Antineuronal nuclear autoantibody type 1 (anti-Hu) and voltage-gated potassium channel complex antibodies were detected in serum. Metaiodobenzylguanidine scan and computed tomography scan of the abdomen showed a localized abdominal mass in the region of the porta hepatis. A diagnosis of occult neuroblastoma was made. Resection of the stage 1 neuroblastoma and treatment with pulsed corticosteroids resulted in resolution of all symptoms and signs. Excessive blinking has rarely been described with neuroblastoma, and, when it is not an isolated finding, it may be a useful clue to this paraneoplastic syndrome. Although voltage-gated potassium channel complex autoimmunity has not been described previously in the setting of neuroblastoma, it is associated with a spectrum of paraneoplastic neurologic manifestations in adults, including peripheral nerve hyperexcitability disorders.

  12. Current strategy for the imaging of neuroblastoma

    International Nuclear Information System (INIS)

    Brisse, H.; Neuenschwander, S.; Edeline, V.; Michon, J.; Zucker, J.M.; Couanet, D.

    2001-01-01

    Advances in the management of neuroblastoma lead radiologists and nuclear medicine specialists to optimize their procedures in order to propose a rational use of their techniques, adjusted to the various clinical presentations and to therapeutic management. The aim of this paper is to assess the imaging procedures for the diagnosis and follow-up of neuroblastoma in children according to current therapeutic European protocols. An imaging strategy at diagnosis is first proposed: optimal assessment of local extension of the primary tumour is made with MRI, or spiral-CT when MRI is not available, for all locations except for abdominal tumours for which CT remains the best imaging modality. Metastatic extension is assessed with mlBG scan and liver sonography. Indications for bone metastasis evaluation with either radiological or radionuclide techniques are detailed. Imaging follow-up during treatment for metastatic or unresectable tumours is described. A check-list of radiological main points to be evaluated before surgery is proposed for localized neuroblastoma. The imaging strategy for the diagnosis of 'occult' neuroblastoma is considered. Finally, we explain the management of neuroblastoma detected during the prenatal or neonatal period. (authors)

  13. Diagnosis and treatment of neuroblastoma using metaiodobenzylguanidine

    International Nuclear Information System (INIS)

    Edeling, C.J.; Frederiksen, P.B.; Kamper, J.; Jeppesen, P.

    1987-01-01

    Neuroblastoma is a lethal and not uncommon tumor in childhood. Early detection and display of the spread of the tumor is highly desirable for proper treatment. Nine children suspected of having neuroblastomas were examined by I-131 metaiodobenzylguanidine (I-131 MIBG) imaging. In two recent studies I-123 metaiodobenzylguanidine (I-123 MIBG) was used. A primary adrenal neuroblastoma was correctly identified in three cases. In two patients additional tumor sites were found. In one patient, who was in complete remission, no pathologic accumulation of I-131 MIBG was found. I-131 MIBG images were also normal in four patients with other types of neoplastic diseases. A boy with multiple metastases was treated with 100 mCi of I-131 MIBG. He developed transient gastrointestinal illness and there was no regression of the tumor deposits. In one girl with a large adrenal neuroblastoma high uptake of I-131 MIBG was observed. She received two therapy doses of I-131 MIBG (35 mCi and 75 mCi) with curative intention giving a total absorbed dose in the tumor of approximately 76 Gy. In spite of high retention of radioactivity in the tumor, regression did not occur, but her general condition was improved. In the present study, images of superior quality were obtained with I-123 MIBG imaging. It is concluded that imaging using I-131 MIBG or I-123 MIBG should be used in both the initial evaluation and the follow-up of children with neuroblastoma

  14. Incidence, Survival, and Treatment of Localized and Metastatic Neuroblastoma in Germany 1979-2015.

    Science.gov (United States)

    Berthold, Frank; Spix, Claudia; Kaatsch, Peter; Lampert, Fritz

    2017-12-01

    A comprehensive clinical long-term survey over the complete spectrum of neuroblatoma disease is lacking in the literature. Our objective was to describe the incidence, risk profiles, therapies, and outcomes for the total cohort of German patients with neuroblastoma including all clinical stages and risk groups. Epidemiological, clinical, and outcome data of neuroblastoma patients who participated in one of the six consecutive national trials between 1979 and 2015 were analyzed retrospectively. Of all German neuroblastoma patients known to the national childhood cancer registry, ninety seven percent enrolled in one of the trials. The absolute neuroblastoma rate has increased slightly, whereas the median age at diagnosis has decreased. Except for the screening period (1995-2000), the risk factors lactate dehydrogenase (LDH), ferritin, chromosome 1p, and the MYCN oncogene have remained largely constant, with the exception of an increase in MYCN amplification at stage 4 for those aged ≥18 months between trials NB97 (27%) and NB2004 (35%). The 10-year overall survival increased in patients with stage 1-3 neuroblastoma from 83 to 91%, for stage 4S from 80 to 85%, and for stage 4 aged ≥18 months from 2 to 38%. The fraction of patients in stages 1-3 who never received chemotherapy (neither for frontline nor at recurrence) increased from 35 to 60%. The proportion of macroscopically complete surgical resections of the primary tumor decreased for the total population as well as for patients with stage 4 aged ≥18 months. The impact of chemotherapy response on the outcome was trial dependent. The overall proportion of toxic death during the time of the protocol therapy was 6% for stage 4 patients aged ≥18 months and 2% for low-/intermediate-risk patients. The most frequently reported late sequelae in stage 4 patients aged ≥18 months were renal dysfunctions, hypothyroidism, major hearing impairment, and second malignancies. The body of data for incidences, risk

  15. Alteration of myocardial metaiodobenzylguanidine uptake after treatment of phaeochromocytoma and neuroblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Suga, Kazuyoshi; Ogasawara, Nobuhiko; Ariga, Misako; Motoyama, Kazumi; Hara, Akiko; Kume, Norihiko; Matsunaga, Naofumi [Department of Radiology, Yamaguchi University School of Medicine, Ube, Yamaguchi (Japan)

    2000-05-01

    The relationships between changes in myocardial uptake of metaiodobenzylguanidine (MIBG) and those in circulating catecholamines and cardiac function after treatment of phaeochromocytoma and neuroblastoma were evaluated. Iodine-123 or iodine-131 MIBG scintigraphy was performed before and after surgical resection and/or chemotherapy for primary tumours in nine patients with phaeochromocytoma and 13 patients with neuroblastoma. Changes in myocardial MIBG uptake after treatment were estimated by the heart-to-upper mediastinum (H/M) uptake ratios on the images obtained 24 h after MIBG injection, which were compared with serum levels of noradrenaline (NA) and adrenaline (A). Cardiac function was assessed by echocardiography, with measurements of the left ventricular ejection fraction (LVEF). Before treatment, eight patients with phaeochromocytoma and three with neuroblastoma showed poor myocardial MIBG uptake, with highly elevated circulating NA and A. Echocardiography, however, did not show cardiac dysfunction in these patients with the exception of two patients with phaeochromocytoma. With normalization of NA and A levels after treatment, all of these patients except for the two with persistent cardiac dysfunction showed restoration of myocardial MIBG uptake. The H/M ratios increased significantly after treatment in both patient groups, i.e. with phaeochromocytoma and with neuroblastoma (P<0.0001 and P<0.05, respectively), and these ratios correlated inversely with circulating NA and A before and after treatment. By contrast, there was no significant correlation between H/M ratios and LVEF in these two groups. These results indicate that suppression of myocardial MIBG uptake usually may not be related to cardiac dysfunction and may be reversible following normalization of excess catecholamine levels after treatment in patients with neuroadrenergic tumours. However, the suppression may persist in the presence of catecholamine-induced cardiac dysfunction. The assessment

  16. Local Control With 21-Gy Radiation Therapy for High-Risk Neuroblastoma

    International Nuclear Information System (INIS)

    Casey, Dana L.; Kushner, Brian H.; Cheung, Nai-Kong V.; Modak, Shakeel; LaQuaglia, Michael P.; Wolden, Suzanne L.

    2016-01-01

    Purpose: To evaluate local control after 21-Gy radiation therapy (RT) to the primary site in patients with high-risk neuroblastoma. Methods and Materials: After receiving dose-intensive chemotherapy and gross total resection (GTR), 246 patients (aged 1.2-17.9 years, median 4.0 years) with high-risk neuroblastoma underwent RT to the primary site at Memorial Sloan Kettering from 2000 to 2014. Radiation therapy consisted of 21 Gy in twice-daily fractions of 1.5 Gy each. Local failure (LF) was correlated with biologic prognostic factors and clinical findings at the time of diagnosis and start of RT. Results: Median follow-up of surviving patients was 6.4 years. Cumulative incidence of LF was 7.1% at 2 years after RT and 9.8% at 5 years after RT. The isolated LF rate was 3.0%. Eighty-six percent of all local failures were within the RT field. Local control was worse in patients who required more than 1 surgical resection to achieve GTR (22.4% vs 8.3%, P=.01). There was also a trend toward inferior local control with MYCN-amplified tumors or serum lactate dehydrogenase ≥1500 U/L (P=.09 and P=.06, respectively). Conclusion: After intensive chemotherapy and maximal surgical debulking, hyperfractionated RT with 21 Gy in high-risk neuroblastoma results in excellent local control. Given the young patient age, concern for late effects, and local control >90%, dose reduction may be appropriate for patients without MYCN amplification who achieve GTR.

  17. Local Control With 21-Gy Radiation Therapy for High-Risk Neuroblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Casey, Dana L. [Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York (United States); Kushner, Brian H.; Cheung, Nai-Kong V.; Modak, Shakeel [Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York (United States); LaQuaglia, Michael P. [Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York (United States); Wolden, Suzanne L., E-mail: woldens@mskcc.org [Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York (United States)

    2016-10-01

    Purpose: To evaluate local control after 21-Gy radiation therapy (RT) to the primary site in patients with high-risk neuroblastoma. Methods and Materials: After receiving dose-intensive chemotherapy and gross total resection (GTR), 246 patients (aged 1.2-17.9 years, median 4.0 years) with high-risk neuroblastoma underwent RT to the primary site at Memorial Sloan Kettering from 2000 to 2014. Radiation therapy consisted of 21 Gy in twice-daily fractions of 1.5 Gy each. Local failure (LF) was correlated with biologic prognostic factors and clinical findings at the time of diagnosis and start of RT. Results: Median follow-up of surviving patients was 6.4 years. Cumulative incidence of LF was 7.1% at 2 years after RT and 9.8% at 5 years after RT. The isolated LF rate was 3.0%. Eighty-six percent of all local failures were within the RT field. Local control was worse in patients who required more than 1 surgical resection to achieve GTR (22.4% vs 8.3%, P=.01). There was also a trend toward inferior local control with MYCN-amplified tumors or serum lactate dehydrogenase ≥1500 U/L (P=.09 and P=.06, respectively). Conclusion: After intensive chemotherapy and maximal surgical debulking, hyperfractionated RT with 21 Gy in high-risk neuroblastoma results in excellent local control. Given the young patient age, concern for late effects, and local control >90%, dose reduction may be appropriate for patients without MYCN amplification who achieve GTR.

  18. Long-Term Outcome and Toxicities of Intraoperative Radiotherapy for High-Risk Neuroblastoma

    International Nuclear Information System (INIS)

    Gillis, Amy M.; Sutton, Elizabeth; DeWitt, Kelly D.; Matthay, Katherine K.; Weinberg, Vivian; Fisch, Benjamin M.; Chan, Albert; Gooding, Charles; Daldrup-Link, Heike; Wara, William M.; Farmer, Diana L.; Harrison, Michael R.; Haas-Kogan, Daphne

    2007-01-01

    Purpose: To review a historical cohort of consecutively accrued patients with high-risk neuroblastoma treated with intraoperative radiotherapy (IORT) to determine the therapeutic effect and late complications of this treatment. Methods and Materials: Between 1986 and 2002, 31 patients with newly diagnosed high-risk neuroblastoma were treated with IORT as part of multimodality therapy. Their medical records were reviewed to determine the outcome and complications. Kaplan-Meier probability estimates of local control, progression-free survival, and overall survival at 36 months after diagnosis were recorded. Results: Intraoperative radiotherapy to the primary site and associated lymph nodes achieved excellent local control at a median follow-up of 44 months. The 3-year estimate of the local recurrence rate was 15%, less than that of most previously published series. Only 1 of 22 patients who had undergone gross total resection developed recurrence at the primary tumor site. The 3-year estimate of local control, progression-free survival, and overall survival was 85%, 47%, and 60%, respectively. Side effects attributable to either the disease process or multimodality treatment were observed in 7 patients who developed either hypertension or vascular stenosis. These late complications resulted in the death of 2 patients. Conclusions: Intraoperative radiotherapy at the time of primary resection offers effective local control in patients with high-risk neuroblastoma. Compared with historical controls, IORT achieved comparable control and survival rates while avoiding many side effects associated with external beam radiotherapy in young children. Although complications were observed, additional analysis is needed to determine the relative contributions of the disease process and specific components of the multimodality treatment to these adverse events

  19. The current contribution of molecular factors to risk estimation in neuroblastoma patients.

    Science.gov (United States)

    Berthold, F; Sahin, K; Hero, B; Christiansen, H; Gehring, M; Harms, D; Horz, S; Lampert, F; Schwab, M; Terpe, J

    1997-10-01

    The association of molecular characteristics with prognosis has been reported, but not their relationship with each other and their impact in the context of known clinical risk factors. In this study, data of 1249 consecutive intent-to-treat-neuroblastoma patients with more than 1 year follow-up were examined by multivariate analysis using loglinear and Cox proportional hazard regression models on a stage-related basis (stages 1-3: 600, 4S: 116, 4: 533). In a first step, risk factors were identified from 18 selected clinical variables, and risk groups defined. The second step investigated whether molecular characteristics (MYCN, LOH 1p, del 1p, CD44, N-ras, NGF-R, bcl-2, APO-1 (CD95)) contributed additional prognostic information to the model. The loglinear model demonstrated several interactions between clinical factors. By the Cox regression model, seven independent clinical risk factors were found for stages 1-3, seven for stage 4 and two for stage 4S. By subsequent introduction of all molecular variables, MYCN amplification only added significant prognostic information to the clinical factors in localised and stage 4 neuroblastoma. The models allowed the definition of risk groups for stages 1-3 patients by age (e beta = 5.09) and MYCN (e beta = 4.26), for stage 4 by MYCN (e beta = 2.78) and number of symptoms (e beta = 2.44) and for stage 4S by platelet count (e beta = 3.91) and general condition (e beta = 2.99). Molecular factors and in particular MYCN contribute significantly to risk estimation. In conjunction with clinical factors, they are powerful tools to define risk groups in neuroblastoma.

  20. Usefulness and limits of ultrasound guided hook-wire positioning for localisation of soft tissue lesions prior to surgery

    International Nuclear Information System (INIS)

    Trenaghi, Alberto; Dal Bosco, Chiara; Talenti, Enrico; Rubaltelli, Enrico; Borsato, Simonetta; Rossi, Carlo Riccardo; Lumachi, Franco

    2005-01-01

    Purpose. The aim of our study was to assess the usefulness of positioning metal wires under ultrasound guidance for localising soft tissue lesions in the preoperative phase. Materials and methods. We studied superficial soft-tissue lesions in 12 patients, using hooked mammographic wires of different lengths. One patient had a multifocal growth of disease which required a double localisation procedure. Correct positioning of the wire was confirmed by ultrasonography. All patients underwent surgery within five hours of hook-wire positioning. Results. Correct wire position was confirmed at surgery in 12 out of 13 procedures. In one case the hook-wire reached the margin of the lesion. In all cases, the preoperative localisation procedure facilitated identification and resection of the masses. Conclusions. In our experience, the main indications for hook-wire positioning before surgery are: marking of small lesions, localisation of lesions in anatomic areas structurally subverted by previous surgery and consequently difficult to detect, guidance for surgical sectioning in order to safeguard the noble structures dose to the lesions [it

  1. CT-assisted localisation of intracranial processes

    Energy Technology Data Exchange (ETDEWEB)

    Luft, C.; Trenkler, J.; Hammer, B.; Valencak, E.

    1986-01-01

    With the software developed for the SOMATOM DRH computerized tomograph it is possible to mix a ROI into the digital radiogram (topogram) for projection of a lesion, such as a tumor, onto the topogram plane; the software also allows an image reconstruction taking the topogram as a reference image (topogram-initiated reconstruction). Combining these two relatively simple methods, and adding distance measurements in two planes, the neurosurgeon has at his disposal an objective CT-assisted means of precisely localising intracranial processes before surgery.

  2. CT-assisted localisation of intracranial processes

    International Nuclear Information System (INIS)

    Luft, C.; Trenkler, J.; Hammer, B.; Valencak, E.

    1986-01-01

    With the software developed for the SOMATOM DRH computerized tomograph it is possible to mix a ROI into the digital radiogram (topogram) for projection of a lesion, such as a tumor, onto the topogram plane; the software also allows an image reconstruction taking the topogram as a reference image (topogram-initiated reconstruction). Combining these two relatively simple methods, and adding distance measurements in two planes, the neurosurgeon has at his disposal an objective CT-assisted means of precisely localising intracranial processes before surgery. (orig.) [de

  3. Localisation in a Growth Model with Interaction

    Science.gov (United States)

    Costa, M.; Menshikov, M.; Shcherbakov, V.; Vachkovskaia, M.

    2018-05-01

    This paper concerns the long term behaviour of a growth model describing a random sequential allocation of particles on a finite cycle graph. The model can be regarded as a reinforced urn model with graph-based interaction. It is motivated by cooperative sequential adsorption, where adsorption rates at a site depend on the configuration of existing particles in the neighbourhood of that site. Our main result is that, with probability one, the growth process will eventually localise either at a single site, or at a pair of neighbouring sites.

  4. The Anderson model for electron localisation

    International Nuclear Information System (INIS)

    Pruisken, A.M.M.; Schaefer, L.

    1982-01-01

    The Anderson model for localisation problems is treated with field theory employing the replica trick. We show that no valid perturbation theory results out of the usual (S2)2 formalism due to mishandling of symmetries. The problem is reformulated in terms of matrix fields. It is shown that the Anderson model asymptotically exhibits an exact local gauge symmetry. Elimination of massive longitudinal components leads to a non-compact sigma model, obtained earlier for the description of electronic disorder. We thus establish that the Anderson model is in the same universality class as Wegner's gauge invariant real matrix model. (orig.)

  5. To localise or to be localised with Wifi in the Hubei museum?

    NARCIS (Netherlands)

    Verbree, E.; Zlatanova, S.; Van Winden, K.; Van der Laan, E.B.; Makri, A.; Taizhou, L.; Haojun, A.

    2013-01-01

    Indoor localisation is in demand for a variety of applications within the built environment. An overall solution based on a single technology has not yet been determined. The aim of this paper is to gain insight on Signal Strength monitoring by a special kind of WiFi Monitors in comparison to the

  6. Impact source localisation in aerospace composite structures

    Science.gov (United States)

    De Simone, Mario Emanuele; Ciampa, Francesco; Boccardi, Salvatore; Meo, Michele

    2017-12-01

    The most commonly encountered type of damage in aircraft composite structures is caused by low-velocity impacts due to foreign objects such as hail stones, tool drops and bird strikes. Often these events can cause severe internal material damage that is difficult to detect and may lead to a significant reduction of the structure’s strength and fatigue life. For this reason there is an urgent need to develop structural health monitoring systems able to localise low-velocity impacts in both metallic and composite components as they occur. This article proposes a novel monitoring system for impact localisation in aluminium and composite structures, which is able to determine the impact location in real-time without a-priori knowledge of the mechanical properties of the material. This method relies on an optimal configuration of receiving sensors, which allows linearization of well-known nonlinear systems of equations for the estimation of the impact location. The proposed algorithm is based on the time of arrival identification of the elastic waves generated by the impact source using the Akaike Information Criterion. The proposed approach was demonstrated successfully on both isotropic and orthotropic materials by using a network of closely spaced surface-bonded piezoelectric transducers. The results obtained show the validity of the proposed algorithm, since the impact sources were detected with a high level of accuracy. The proposed impact detection system overcomes current limitations of other methods and can be retrofitted easily on existing aerospace structures allowing timely detection of an impact event.

  7. [Morphea or juvenile localised scleroderma: Case report].

    Science.gov (United States)

    Strickler, Alexis; Gallo, Silvanna; Jaramillo, Pedro; de Toro, Gonzalo

    2016-01-01

    Morphea or juvenile localised scleroderma (JLS) is an autoimmune, inflammatory, chronic, slowly progressive connective tissue disease of unknown cause that preferably affects skin and underlying tissues. To report a case of Juvenil Localised scleroderma in an 8-year old girl, contributing to an early diagnosis and treatment. The case is presented of an 8 year-old girl who presented with indurated hypopigmented plaques, of linear distribution in the right upper extremity of two years onset, together with papery texture hyperpigmented indurated plaques with whitish areas of thinned skin in right lower extremity, and leg and ankle swelling. The clinical features and diagnostic tests, including histology were compatible with linear and pansclerotic JLS. She started with immunosuppressive therapy, physiotherapy, and occupational therapy. We report a case of linear and pansclerotic ELJ type, in which there was a 2 year delay in diagnosis, however the response to treatment was positive as expected. Copyright © 2016 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  8. Periostitis and localised myositis in polyarteritis nodosa

    International Nuclear Information System (INIS)

    Macdonald, W.B.G.; Blake, M.P.

    2003-01-01

    Full text: A 20-year-old man with previously diagnosed polyarteritis nodosa was referred for a bone scan to investigate longstanding knee and lower leg pain. The patient's symptoms worsened with any reduction of steroid dose and his physician was concerned about avascular necrosis of the hips. Plain x-rays of the lower limbs were normal. The blood pool images showed bilaterally increased activity in the anterior muscle compartments of the lower legs, suggestive of localised myositis. Three-hour delayed images showed widespread, increased subperiosteal activity with no evidence of avascular necrosis. Subsequent MRI scanning showed patchy muscle enhancement in both lower legs, also typical of myositis. A muscle biopsy was performed which demonstrated features of both myositis and vasculitis. The patient remains dependent on high-dose steroids for symptom relief. Localised myositis has previously been reported in polyarteritis nodosa and is a recognised, albeit rare, complication of the disorder, the basis of which is not well understood. Diagnostic muscle biopsy should be directed at involved muscle groups, which are best detected with MRI. Lower limb periostitis is well described in polyarteritis nodosa and may result in gross deformity. Several cases have previously been reported in the literature based on radiographic abnormalities, which were not present in our patient. Bone scanning demonstrated the sub-periosteal activity well in our subject and is suggested as a useful investigation in patients with polyarteritis nodosa who complain of lower limb pain. Copyright (2003) The Australian and New Zealand Society of Nuclear Medicine Inc

  9. Neonatal acute megakaryoblastic leukemia mimicking congenital neuroblastoma

    OpenAIRE

    Kawasaki, Yukako; Makimoto, Masami; Nomura, Keiko; Hoshino, Akihiro; Hamashima, Takeru; Hiwatari, Mitsuteru; Nakazawa, Atsuko; Takita, Junko; Yoshida, Taketoshi; Kanegane, Hirokazu

    2014-01-01

    Key Clinical Message We describe a neonate with abdominal distension, massive hepatomegaly, and high serum neuron-specific enolase level suggestive of congenital neuroblastoma. The patient died of pulmonary hemorrhage after therapy. Autopsy revealed that the tumor cells in the liver indicated acute megakaryocytic leukemia with the RBM15-MKL1 fusion gene.

  10. Monoclonal Antibody Therapy for Advanced Neuroblastoma

    Science.gov (United States)

    NCI is sponsoring two clinical trials of a monoclonal antibody called ch14.18, in combination with other drugs, to see if the antibody may be helpful for children or young adults (up to age 21) with relapsed or refractory neuroblastoma.

  11. Symmetry breaking in human neuroblastoma cells

    Science.gov (United States)

    Izumi, Hideki; Kaneko, Yasuhiko

    2014-01-01

    Asymmetric cell division (ACD) is a characteristic of cancer stem cells, which exhibit high malignant potential. However, the cellular mechanisms that regulate symmetric (self-renewal) and asymmetric cell divisions are mostly unknown. Using human neuroblastoma cells, we found that the oncosuppressor protein tripartite motif containing 32 (TRIM32) positively regulates ACD. PMID:27308367

  12. An innovative localisation algorithm for railway vehicles

    Science.gov (United States)

    Allotta, B.; D'Adamio, P.; Malvezzi, M.; Pugi, L.; Ridolfi, A.; Rindi, A.; Vettori, G.

    2014-11-01

    In modern railway automatic train protection and automatic train control systems, odometry is a safety relevant on-board subsystem which estimates the instantaneous speed and the travelled distance of the train; a high reliability of the odometry estimate is fundamental, since an error on the train position may lead to a potentially dangerous overestimation of the distance available for braking. To improve the odometry estimate accuracy, data fusion of different inputs coming from a redundant sensor layout may be used. The aim of this work has been developing an innovative localisation algorithm for railway vehicles able to enhance the performances, in terms of speed and position estimation accuracy, of the classical odometry algorithms, such as the Italian Sistema Controllo Marcia Treno (SCMT). The proposed strategy consists of a sensor fusion between the information coming from a tachometer and an Inertial Measurements Unit (IMU). The sensor outputs have been simulated through a 3D multibody model of a railway vehicle. The work has provided the development of a custom IMU, designed by ECM S.p.a, in order to meet their industrial and business requirements. The industrial requirements have to be compliant with the European Train Control System (ETCS) standards: the European Rail Traffic Management System (ERTMS), a project developed by the European Union to improve the interoperability among different countries, in particular as regards the train control and command systems, fixes some standard values for the odometric (ODO) performance, in terms of speed and travelled distance estimation. The reliability of the ODO estimation has to be taken into account basing on the allowed speed profiles. The results of the currently used ODO algorithms can be improved, especially in case of degraded adhesion conditions; it has been verified in the simulation environment that the results of the proposed localisation algorithm are always compliant with the ERTMS requirements

  13. Enantioselective cellular localisation of europium(iii) coordination complexes.

    Science.gov (United States)

    Frawley, Andrew T; Linford, Holly V; Starck, Matthieu; Pal, Robert; Parker, David

    2018-01-28

    The selective mitochondrial localisation of the Λ enantiomer of three different emissive europium(iii) complexes in NIH 3T3 and MCF7 cells contrasts with the behaviour of the Δ enantiomer, for which a predominant lysosomal localisation was observed by confocal microscopy. In each case, cell uptake occurs via macropinocytosis.

  14. Differences in finger localisation performance of patients with finger agnosia

    NARCIS (Netherlands)

    Anema, H.A.; Kessels, R.P.C.; de Haan, E.H.F.; Kappelle, L.J.; Leijten, F.S.; van Zandvoort, M.J.E.; Dijkerman, H.C.

    2008-01-01

    Several neuropsychological studies have suggested parallel processing of somatosensory input when localising a tactile stimulus on one's own by pointing towards it (body schema) and when localising this touched location by pointing to it on a map of a hand (body image). Usually these reports

  15. Differences in finger localisation performance of patients with finger agnosia

    NARCIS (Netherlands)

    Anema, H.A.; Kessels, R.P.C.; Haan, E.H.F. de; Kappelle, L.J.; Leijten, F.S.S.; Zandvoort, M.J.E. van; Dijkerman, H.C.

    2008-01-01

    Several neuropsychological studies have suggested parallel processing of somatosensory input when localising a tactile stimulus on ones own by pointing towards it (body schema) and when localising this touched location by pointing to it on a map of a hand (body image). Usually these reports describe

  16. Differences in finger localisation performance of patients with finger agnosia.

    NARCIS (Netherlands)

    Anema, H.A.; Kessels, R.P.C.; Haan, E.H.F. de; Kappelle, L.J.; Leijten, F.S.S.; Zandvoort, M.J. Van; Dijkerman, H.C.

    2008-01-01

    Several neuropsychological studies have suggested parallel processing of somatosensory input when localising a tactile stimulus on one's own by pointing towards it (body schema) and when localising this touched location by pointing to it on a map of a hand (body image). Usually these reports

  17. Localisation system in wireless sensor networks using ns-2

    CSIR Research Space (South Africa)

    Abu-Mahfouz, Adnan M

    2012-04-01

    Full Text Available -1 /************************************************************************** ********** * * File: readme.asn * * Author: Adnan Abu-Mahfouz * * Date: March 2012 * * Description: Localisation system in wireless sensor networks using ns-2... *************************************************************************** *********/ /************************************************************************** *************************************************************************** *****/ 1. Introduction: ns-2 contains several flexible features that encourage researchers to use ns-2 to investigate the characteristics of wireless sensor networks (WSNs). However, to implement and evaluate localisation algorithms, the current ns- 2...

  18. Amelogenesis imperfecta and localised aggressive periodontitis: A rare clinical entity

    Directory of Open Access Journals (Sweden)

    Gayatri Gundannavar

    2013-01-01

    Full Text Available This case report presents two female patients whose chief complaint was discoloration of teeth. On careful clinical examination it was found that the patients had features of amelogenesis imperfecta and localised aggressive periodontitis. This article will give an insight of clinical and radiographic features of amelogenesis imperfecta with localised aggressive periodontitis, which is a rare clinical entity.

  19. Reaction-Diffusion Automata Phenomenology, Localisations, Computation

    CERN Document Server

    Adamatzky, Andrew

    2013-01-01

    Reaction-diffusion and excitable media are amongst most intriguing substrates. Despite apparent simplicity of the physical processes involved the media exhibit a wide range of amazing patterns: from target and spiral waves to travelling localisations and stationary breathing patterns. These media are at the heart of most natural processes, including morphogenesis of living beings, geological formations, nervous and muscular activity, and socio-economic developments.   This book explores a minimalist paradigm of studying reaction-diffusion and excitable media using locally-connected networks of finite-state machines: cellular automata and automata on proximity graphs. Cellular automata are marvellous objects per se because they show us how to generate and manage complexity using very simple rules of dynamical transitions. When combined with the reaction-diffusion paradigm the cellular automata become an essential user-friendly tool for modelling natural systems and designing future and emergent computing arch...

  20. Feasibility of magnetic marker localisation for non-palpable breast cancer

    NARCIS (Netherlands)

    Schermers, B.; van der Hage, Jos A.; Loo, C.E.; Vrancken Peeters, M.T.F.D.; Winter-Warnars, H. A.O.; Duijnhoven, F.H.; ten Haken, B.; Muller, S.H.; Ruers, T. J.M.

    2017-01-01

    Objectives Accurate tumour localisation is essential for breast-conserving surgery of non-palpable tumours. Current localisation technologies are associated with disadvantages such as logistical challenges and migration issues (wire guided localisation) or legislative complexities and high

  1. Treatment of extradural paraspinal neuroblastoma with an intraspinal component

    International Nuclear Information System (INIS)

    Ho, K.S.Y.; Wara, W.M.; Ablin, A.R.

    1982-01-01

    Neuroblastoma originates from neural crest cells and can be found wherever sympathetic neural tissue is normally located. When the tumor arises from a paraspinal sympathetic ganglion, it has a propensity to extend through the intervertebral foramina, producing an extradural paraspinal neuroblastoma with an interspinal component (''dumbell'' neuroblastoma) which may result in spinal cord compression. The records of all children with neuroblastomas referred to the UCSF Department of Radiation Oncology and the Division of Pediatric Oncology from January 1, 1970, to December 31, 1979, are reviewed in this report. Patients who at initial presentation had a ''dumbell'' neuroblastoma were selected for study. Neuroblastoma was diagnosed histologically in all patients except one. Disease-free interval and length of survival was measured from the date of completion of radiotherapy, mostly after surgery. The results of diagnostic X-rays and laboratory studies are shown. Radiotherapeutic doses and results are tabulated. (Auth.)

  2. MMSET is highly expressed and associated with aggressiveness in neuroblastoma

    DEFF Research Database (Denmark)

    Hudlebusch, Heidi Rye; Skotte, Julie; Santoni-Rugiu, Eric

    2011-01-01

    tumor types as well. We have performed immunohistochemical staining of tissue microarrays and found that MMSET protein is frequently and highly expressed in neuroblastoma (MMSET positive in 75% of neuroblastomas, n=164). The expression level of MMSET in neuroblastomas was significantly associated...... with poor survival, negative prognostic factors, and metastatic disease. Moreover, a subset of neuroblastomas for which pre- and post-chemotherapy biopsies were available displayed a strong decrease in MMSET protein levels after chemotherapy. In agreement with neuroblastomas becoming more differentiated...... after treatment, we show that retinoic acid-induced differentiation of human neuroblastoma cells in vitro also leads to a strong decrease in MMSET levels. Furthermore, we demonstrate that the high levels of MMSET in normal neural progenitor cells are strongly downregulated during differentiation...

  3. Immunostimulatory sutures that treat local disease recurrence following primary tumor resection

    Energy Technology Data Exchange (ETDEWEB)

    Intra, Janjira; Zhang Xueqing; Salem, Aliasger K [Division of Pharmaceutics, College of Pharmacy, University of Iowa, Iowa City, IA 52242 (United States); Williams, Robin L; Zhu Xiaoyan [Department of Surgery, Roy J and Lucille Carver College of Medicine, University of Iowa, Iowa City, IA 52242 (United States); Sandler, Anthony D, E-mail: aliasger-salem@uiowa.edu [Department of Surgery and Center for Cancer and Immunology Research, Children' s National Medical Center, Washington DC 20010 (United States)

    2011-02-15

    Neuroblastoma is a common childhood cancer that often results in progressive minimal residual disease after primary tumor resection. Cytosine-phosphorothioate-guanine oligonucleotides (CpG ODN) have been reported to induce potent anti-tumor immune responses. In this communication, we report on the development of a CpG ODN-loaded suture that can close up the wound following tumor excision and provide sustained localized delivery of CpG ODN to treat local disease recurrence. The suture was prepared by melt extruding a mixture of polylactic acid-co-glycolic acid (PLGA 75:25 0.47 dL g{sup -1}) pellets and CpG ODN 1826. Scanning electron microscopy images showed that the sutures were free of defects and cracks. UV spectrophotometry measurements at 260 nm showed that sutures provide sustained release of CpG ODN over 35 days. Syngeneic female A/J mice were inoculated subcutaneously with 1 x 10{sup 6} Neuro-2a murine neuroblastoma wild-type cells and tumors were grown between 5 to 10 mm before the tumors were excised. Wounds from the tumor resection were closed using CpG ODN-loaded sutures and/or polyglycolic acid Vicryl suture. Suppression of neuroblastoma recurrence and mouse survival were significantly higher in mice where wounds were closed using the CpG ODN-loaded sutures relative to all other groups. (communication)

  4. The association of congenital neuroblastoma and congenital heart disease

    International Nuclear Information System (INIS)

    Bellah, R.; D'Andrea, A.; Children's Hospital, Boston, MA; Darillis, E.; Fellows, K.E.

    1989-01-01

    Several authors have reported an association between neuroblastoma and congenital heart disease; others contend that, unlike specific wellknown associations between malignancy and congenital defects (Wilm's tumor and aniridia, leukemia and Down's syndrome), no real relationship exists. We present three cases of cyanotic congenital heart disease in which subclinical neuroblastoma was found. We speculate that abnormal neural crest cell migration and development may be a common link between cardiac malformations and congenital neuroblastoma. (orig.)

  5. Marrow Derived Antibody Library for the Treatment of Neuroblastoma

    Science.gov (United States)

    2015-12-01

    Award Number: W81XWH-12-1-0332 TITLE: Marrow-Derived Antibody Library for the Treatment of Neuroblastoma PRINCIPAL INVESTIGATOR: Giselle...Marrow-Derived Antibody Library for Treatment of Neuroblastoma 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S...to Spectrum Health. 14. ABSTRACT Neuroblastoma (NB) is the most common solid tumor in children, which accounts for 15% of all pediatric cancer deaths

  6. Magnetic resonance imaging of olfactory neuroblastoma

    International Nuclear Information System (INIS)

    Iio, Mitsuhiro; Homma, Akihiro; Furuta, Yasushi; Fukuda, Satoshi

    2006-01-01

    Olfactory neuroblastoma is an uncommon intranasal tumor originating from olfactory neuroepithelium. Despite the development of electron microscopy and immunohistochemical testing, the pathological diagnosis of this tumor is still difficult because of the wide range of histological features. Magnetic resonance imaging (MR) of this tumor and the pattern of contrast enhancement have not been well described. The purpose of this report was to analyze the MR characteristics of olfactory neuroblastomas. The MR signal, pattern of contrast enhancement, and correlation with high-resolution computed tomography (CT) imaging were examined. Seventeen patients with olfactory neuroblastoma were treated at Hokkaido University Hospital and a related hospital during the past 25 years. MR images taken in 12 patients and CT images taken in 9 patients with histologically confirmed olfactory neuroblastoma were retrospectively reviewed. Compared with brain gray matter, 11 tumors were hypointense on T1-weighted images, 9 homogeneously and 2 heterogeneously. Eight tumors were hyperintense on T2-weighted images, 3 homogeneously and 5 heterogeneously, although their appearance was less intense than that of sinusitis. Gadolinium enhancement was moderate in one case and marked in 10 of the 11 cases, 9 homogeneously and 2 heterogeneously. Nine of the 11 tumors showed smooth regular shaped margins; 2 of these tumors exhibited irregular infiltrating margins on gadolinium-enhanced images, compared to the pre-contrast T1-weighted images. Eight of the 11 tumors had clearly demarcated margins, while 3 of the 11 tumors did not exhibit gadolinium enhancement. Six of the 12 cases (50%) exhibited intracranial cysts on the gadolinium-enhanced images. T2-weighted or gadolinium-enhanced images successfully distinguished sinusitis from tumors in 4 cases whereas the CT images failed. Gadolinium enhancement, particularly in the tangential plane, demonstrated intracranial extension not apparent on the CT images

  7. Environment Mediated Drug Resistance in Neuroblastoma

    Science.gov (United States)

    2015-12-01

    activate STAT3 and MYC in neuroblastomas independently of IL6). Figure 9: Effect of IL-6 knockout crossing with NB- Tag mice. (A) MRI of abdominal...production. (D) Representative MRI images of NB-Tag and NB- Tag/IL-6KO pre-chemotherapy, post 3 and 6 weeks of chemotherapy. Task 6. Contribution of bone...described (16). Cells were lysed in radioimmunoprecipitation assay (RIPA) buffer supplemented with 1 tablet of complete mini-EDTA protease inhibitor

  8. Importance of neoadjuvant chemotherapy in olfactory neuroblastoma treatment: Series report and literature review.

    Science.gov (United States)

    Bartel, Ricardo; Gonzalez-Compta, Xavier; Cisa, Enric; Cruellas, Francesc; Torres, Alberto; Rovira, Aleix; Manos, Manel

    2017-10-20

    Olfactory neuroblastoma (ONB) is a rare entity that constitutes less than 5% of nasosinusal malignancies. Mainstream treatment consists in surgical resection+/-adjuvant radiotherapy. By exposing results observed with apparition of new therapeutic options as neoadjuvant chemotherapy, the objective is to evaluate a series and a review of the current literature. A retrospective review was conducted including patients diagnosed and followed-up for ONB from 2008 to 2015 in our institution. 9 patients were included. Mean follow-up of 52.5 months (range 10-107). Kadish stage: A, 1 patient (11.1%) treated with endoscopic surgery; B, 2 patients (22.2%) treated with endoscopic surgery (one of them received adjuvant radiotherapy); C, 6 patients (66.7%), 4 patients presented intracranial extension and were treated with neoadjuvant chemotherapy followed by surgery and radiotherapy. The other 2 patients presented isolated orbital extension, treated with radical surgery (endoscopic or craniofacial resection) plus radiotherapy. The 5-year disease free and overall survival observed was 88.9%. Neoadjuvant chemotherapy could be an effective treatment for tumor reduction, improving surgical resection and reducing its complications. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. All rights reserved.

  9. Percentage tumor necrosis following chemotherapy in neuroblastoma correlates with MYCN status but not survival.

    Science.gov (United States)

    Bomken, Simon; Davies, Beverley; Chong, Leeai; Cole, Michael; Wood, Katrina M; McDermott, Michael; Tweddle, Deborah A

    2011-03-01

    The percentage of chemotherapy-induced necrosis in primary tumors corresponds with outcome in several childhood malignancies, including high-risk metastatic diseases. In this retrospective pilot study, the authors assessed the importance of postchemotherapy necrosis in high-risk neuroblastoma with a histological and case notes review of surgically resected specimens. The authors reviewed all available histology of 31 high-risk neuroblastoma cases treated with COJEC (dose intensive etoposide and vincristine with either cyclophosphamide, cisplatin or carboplatin) or OPEC/OJEC (etoposide, vincristine and cyclophosphamide with alternating cisplatin [OPEC] or carboplatin [OJEC]) induction chemotherapy in 2 Children's Cancer & Leukaemia Group (CCLG) pediatric oncology centers. The percentage of postchemotherapy necrosis was assessed and compared with MYCN amplification status and overall survival. The median percentage of postchemotherapy tumor necrosis was 60%. MYCN status was available for 28 cases, of which 12 were amplified (43%). Survival in cases with ≥ 60% necrosis or ≥ 90% necrosis was not better than those with less necrosis, nor was percentage necrosis associated with survival using Cox regression. However, MYCN-amplified tumors showed a higher percentage of necrosis than non-MYCN-amplified tumors, 71.3% versus 37.2% (P = .006). This effect was not related to prechemotherapy necrosis and did not confer improved overall survival. Postchemotherapy tumor necrosis is higher in patients with MYCN amplification. In this study, postchemotherapy necrosis did not correlate with overall survival and should not lead to modification of postoperative treatment. However, these findings need to be confirmed in a larger prospective study of children with high-risk neuroblastoma.

  10. Small bowel resection

    Science.gov (United States)

    ... Ileostomy and your diet Ileostomy - caring for your stoma Ileostomy - changing your pouch Ileostomy - discharge Ileostomy - what to ask your doctor Low-fiber diet Preventing falls Small bowel resection - discharge Surgical wound care - open Types of ileostomy Ulcerative colitis - discharge When ...

  11. Large bowel resection

    Science.gov (United States)

    ... blockage in the intestine due to scar tissue Colon cancer Diverticular disease (disease of the large bowel) Other reasons for bowel resection are: Familial polyposis (polyps are growths on the lining of the colon or rectum) Injuries that damage the large bowel ...

  12. Neuroblastoma occurring in a 38-year old Nigerian man: a rare finding

    Directory of Open Access Journals (Sweden)

    Aloy Aghaji

    2009-07-01

    Full Text Available Neuroblastoma (NB is a common malignancy in children, but rarely occurs in adults. Accepted unfavorable prognostic factors include age over one year, low histological grade and advanced stage, MYCN amplification, chromosomal aberrations, elevations of neuron specific enolase and lactate dehydrogenase, and increased catecholamine metabolites in urine or serum. In adults, abdomen/retroperitoneum are the primary sites and in children the adrenal gland. We report a 38-year old civil servant who presented at our urology clinic on the 21st of December 2007 with a six month history of right flank dull pain which was worse on walking and relieved by rest, hypertension and a large right retroperitoneal mass. Tumor resection revealed a grade III NB. Chemotherapy using a combination of vincristine, adriamycin and cyclophosphamide was started. Follow-up showed regression of the mass initially with a relapse after patient absconded for three months. He resurfaced with new masses and he had a repeat chemotherapy with disappearance of the masses and is currently undergoing further treatment. To our knowledge this is the only report of NB in an adult registered so far in Nigeria and perhaps the whole of Africa. Currently, there are no standard treatment guidelines for patients with NB in adulthood. This study emphasizes the need for a standard treatment regime for adult onset neuroblastoma and its recognition as a possible differential in intra-abdominal mass in adults.

  13. Generalised two target localisation using passive monopulse radar

    KAUST Repository

    Jardak, Seifallah

    2017-04-07

    The simultaneous lobing technique, also known as monopulse technique, has been widely used for fast target localisation and tracking purposes. Many works focused on accurately localising one or two targets lying within a narrow beam centred around the monopulse antenna boresight. In this study, a new approach is proposed, which uses the outputs of four antennas to rapidly localise two point targets present in the hemisphere. If both targets have the same elevation angle, the proposed scheme cannot detect them. To detect such targets, a second set of antennas is required. In this study, to detect two targets at generalised locations, the antenna array is divided into multiple overlapping sets each of four antennas. Two algorithms are proposed to combine the outputs from multiple sets and improve the detection performance. Simulation results show that the algorithm is able to localise both targets with <;2° mean square error in azimuth and elevation.

  14. Is the Pauli exclusion principle the origin of electron localisation?

    Science.gov (United States)

    Rincón, Luis; Torres, F. Javier; Almeida, Rafael

    2018-03-01

    In this work, we inquire into the origins of the electron localisation as obtained from the information content of the same-spin pair density, γσ, σ(r2∣r1). To this end, we consider systems of non-interacting and interacting identical Fermions contained in two simple 1D potential models: (1) an infinite potential well and (2) the Kronig-Penney periodic potential. The interparticle interaction is considered through the Hartree-Fock approximation as well as the configuration interaction expansion. Morover, the electron localisation is described through the Kullback-Leibler divergence between γσ, σ(r2∣r1) and its associated marginal probability. The results show that, as long as the adopted method properly includes the Pauli principle, the electronic localisation depends only modestly on the interparticle interaction. In view of the latter, one may conclude that the Pauli principle is the main responsible for the electron localisation.

  15. Paraneoplastic limbic encephalitis associated with mixed olfactory neuroblastoma and craniopharyngioma: A case report and literature review.

    Science.gov (United States)

    Nagafuji, Hiroshi; Yokoi, Hidenori; Fujiwara, Masachika; Sato, Dai; Saito, Koichiro

    2018-06-01

    Paraneoplastic limbic encephalitis (PLE) is a rare disorder of the nervous system associated with malignant disease. It has a subacute onset with the following symptoms: cognitive dysfunction, seizures, irritability, hallucinations, and short-term memory loss. Herein, we report the case of a 35-year-old man with PLE, an olfactory neuroblastoma (ONB) admixed with craniopharyngioma, and serum anti-Hu antibodies. The patient presented with generalized seizures, short-term memory loss, and a polypoid mass located high in the nasal cavity. He underwent surgical resection of the tumor and postoperative chemoradiotherapy with concurrent intra-arterial cisplatin administration. Pathological examination indicated an ONB admixed with craniopharyngioma. The patient's neurological symptoms gradually diminished after surgery. No evidence of recurrence was observed during a 4-year follow-up. We reported a histologically unusual heterogeneous tumor that comprised ONB and craniopharyngioma. This is the first reported case of PLE with anti-Hu antibodies possibly associated with ONB admixed with craniopharyngioma.

  16. Rho-associated kinase is a therapeutic target in neuroblastoma.

    Science.gov (United States)

    Dyberg, Cecilia; Fransson, Susanne; Andonova, Teodora; Sveinbjörnsson, Baldur; Lännerholm-Palm, Jessika; Olsen, Thale K; Forsberg, David; Herlenius, Eric; Martinsson, Tommy; Brodin, Bertha; Kogner, Per; Johnsen, John Inge; Wickström, Malin

    2017-08-08

    Neuroblastoma is a peripheral neural system tumor that originates from the neural crest and is the most common and deadly tumor of infancy. Here we show that neuroblastoma harbors frequent mutations of genes controlling the Rac/Rho signaling cascade important for proper migration and differentiation of neural crest cells during neuritogenesis. RhoA is activated in tumors from neuroblastoma patients, and elevated expression of Rho-associated kinase (ROCK)2 is associated with poor patient survival. Pharmacological or genetic inhibition of ROCK1 and 2, key molecules in Rho signaling, resulted in neuroblastoma cell differentiation and inhibition of neuroblastoma cell growth, migration, and invasion. Molecularly, ROCK inhibition induced glycogen synthase kinase 3β-dependent phosphorylation and degradation of MYCN protein. Small-molecule inhibition of ROCK suppressed MYCN -driven neuroblastoma growth in TH- MYCN homozygous transgenic mice and MYCN gene-amplified neuroblastoma xenograft growth in nude mice. Interference with Rho/Rac signaling might offer therapeutic perspectives for high-risk neuroblastoma.

  17. Targeted BCL2 inhibition effectively inhibits neuroblastoma tumour growth

    NARCIS (Netherlands)

    Lamers, Fieke; Schild, Linda; den Hartog, Ilona J. M.; Ebus, Marli E.; Westerhout, Ellen M.; Ora, Ingrid; Koster, Jan; Versteeg, Rogier; Caron, Huib N.; Molenaar, Jan J.

    2012-01-01

    Genomic aberrations of key regulators of the apoptotic pathway have hardly been identified in neuroblastoma. We detected high BCL2 mRNA and protein levels in the majority of neuroblastoma tumours by Affymetrix expression profiling and Tissue Micro Array analysis. This BCL2 mRNA expression is

  18. Neuroblastoma Treatment (PDQ®)—Health Professional Version

    Science.gov (United States)

    Neuroblastoma treatment depends on the assigned risk category (low, intermediate, high, stage 4S). Get detailed information about the genomic/biologic features, presentation, diagnosis/staging, risk groups, prognosis and treatment of newly diagnosed and recurrent neuroblastoma in this summary for clinicians.

  19. Immunohistochemical localisation of d-β-aspartic acid in pingueculae

    OpenAIRE

    Kaji, Y; Oshika, T; Okamoto, F; Fujii, N

    2009-01-01

    Background: D-β-Aspartic acid residues, which are biologically uncommon, have been reported to accumulate in various proteins of the living body with age. In the present study, D-β-aspartic acid-containing proteins were found to be localised in pingueculae, which represent one of the most prominent age-related ocular changes.Methods: Surgical specimens of conjunctivae with or without pingueculae were obtained from eight patients. Immunohistochemical localisation of D-β-aspartic acid-containin...

  20. Indoor Localisation Based on GSM Signals: Multistorey Building Study

    Directory of Open Access Journals (Sweden)

    Rafał Górak

    2016-01-01

    Full Text Available Among the accurate indoor localisation systems that are using WiFi, Bluetooth, or infrared technologies, the ones that are based on the GSM rely on a stable external infrastructure that can be used even in an emergency. This paper presents an accurate GSM indoor localisation system that achieves a median error of 4.39 metres in horizontal coordinates and up to 64 percent accuracy in floor prediction (for 84 percent of cases the floor prediction is mistaken by not more than a single floor. The test and reference measurements were made inside a six-floor academic building, with an irregular shape, whose dimensions are around 50 metres by 70 metres. The localisation algorithm uses GSM signal readings from the 7 strongest cells available in the GSM standard (or fewer, if fewer than 7 are available. We estimate the location by a three-step method. Firstly, we propose a point localisation solution (i.e., localisation based on only one measurement. Then, by applying the central tendency filters and the Multilayer Perceptron, we build a localisation system that uses a sequence of estimations of current and past locations. We also discuss major accuracy factors such as the number of observed signals or the types of spaces in the building.

  1. International consensus for neuroblastoma molecular diagnostics: report from the International Neuroblastoma Risk Group (INRG) Biology Committee

    Science.gov (United States)

    Ambros, P F; Ambros, I M; Brodeur, G M; Haber, M; Khan, J; Nakagawara, A; Schleiermacher, G; Speleman, F; Spitz, R; London, W B; Cohn, S L; Pearson, A D J; Maris, J M

    2009-01-01

    Neuroblastoma serves as a paradigm for utilising tumour genomic data for determining patient prognosis and treatment allocation. However, before the establishment of the International Neuroblastoma Risk Group (INRG) Task Force in 2004, international consensus on markers, methodology, and data interpretation did not exist, compromising the reliability of decisive genetic markers and inhibiting translational research efforts. The objectives of the INRG Biology Committee were to identify highly prognostic genetic aberrations to be included in the new INRG risk classification schema and to develop precise definitions, decisive biomarkers, and technique standardisation. The review of the INRG database (n=8800 patients) by the INRG Task Force finally enabled the identification of the most significant neuroblastoma biomarkers. In addition, the Biology Committee compared the standard operating procedures of different cooperative groups to arrive at international consensus for methodology, nomenclature, and future directions. Consensus was reached to include MYCN status, 11q23 allelic status, and ploidy in the INRG classification system on the basis of an evidence-based review of the INRG database. Standardised operating procedures for analysing these genetic factors were adopted, and criteria for proper nomenclature were developed. Neuroblastoma treatment planning is highly dependant on tumour cell genomic features, and it is likely that a comprehensive panel of DNA-based biomarkers will be used in future risk assignment algorithms applying genome-wide techniques. Consensus on methodology and interpretation is essential for uniform INRG classification and will greatly facilitate international and cooperative clinical and translational research studies. PMID:19401703

  2. Analysis of 1;17 translocation breakpoints in neuroblastoma: implications for mapping of neuroblastoma genes

    NARCIS (Netherlands)

    van Roy, N.; Laureys, G.; van Gele, M.; Opdenakker, G.; Miura, R.; van der Drift, P.; Chan, A.; Versteeg, R.; Speleman, F.

    1997-01-01

    Deletions and translocations resulting in loss of distal 1p-material are known to occur frequently in advanced neuroblastomas. Fluorescence in situ hybridisation (FISH) showed that 17q was most frequently involved in chromosome 1p translocations. A review of the literature shows that 10 of 27 cell

  3. Intravenous digital subtraction angiography for the evaluation of renal artery blood flow following the removal of a neuroblastoma

    International Nuclear Information System (INIS)

    Yamagiwa, Iwao; Obata, Kazuya; Saito, Hiroyuki; Washio, Masahiko

    1994-01-01

    There have been several reports of acute renal failure following the resection of an abdominal neuroblastoma combined with ipsilateral nephrectomy as well as the atrophy or disappearance of an unresected kidney after tumor resection. Spasms or thrombosis of the renal artery during tumor excision are considered to be the major cause. Since 1989, intravenous digital subtraction angiography (IVDSA) has been used to evaluate the renal artery blood flow immediately following surgery in seven patients with abdominal neuroblastomas. IVDSA was performed using a central venous catheter inserted prior to surgery. In all seven patients, IVDSA provided clear images for the evaluation of renal artery blood flow. In one of the two patients whose kidneys briefly became cyanosed during tumor excision, IVDSA demonstrated an occlusion of the renal artery and prompt measures could be taken to reestablish the blood flow. No complications of IVDSA occurred in any of the seven patients. IVDSA using a central venous catheter was thus considered to be useful for evaluating the renal artery blood flow in patients with a suspected renal artery blood flow disturbance without any risk of complications, and this modality obviated the need for intraarterial angiography. (author)

  4. Radiation Therapy to the Primary and Postinduction Chemotherapy MIBG-Avid Sites in High-Risk Neuroblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Mazloom, Ali; Louis, Chrystal U.; Nuchtern, Jed; Kim, Eugene; Russell, Heidi; Allen-Rhoades, Wendy; Krance, Robert; Paulino, Arnold C., E-mail: apaulino@mdanderson.org

    2014-11-15

    Purpose: Although it is generally accepted that consolidation therapy for neuroblastoma includes irradiation of the primary site and any remaining metaiodobenzylguanidine (MIBG)-avid metastatic sites, limited information has been published regarding the efficacy of this approach. Methods and Materials: Thirty patients with high-risk neuroblastoma were treated at 1 radiation therapy (RT) department after receiving 5 cycles of induction chemotherapy and resection. All patients had at least a partial response after induction therapy, based upon international neuroblastoma response criteria. The primary sites were treated with 24 to 30 Gy whereas the MIBG-avid metastatic sites were treated with 24 Gy. RT was followed by high-dose chemotherapy with autologous stem cell rescue and 6 months of cis-retinoic acid. Results: The 5-year progression-free survival (PFS) and overall survival (OS) rates were 48% and 59%, respectively. The 5-year locoregional control at the primary site was 84%. There were no differences in locoregional control according to degree of primary surgical resection. The 5-year local control rate for metastatic sites was 74%. The 5-year PFS rates for patients with 0, 1, 2, and >3 postinduction MIBG sites were 66%, 57%, 20%, and 0% (P<.0001), respectively, whereas 5-year OS rates were 80%, 57%, 50%, and 0%, respectively (P<.0001). Conclusions: RT to the primary site and postinduction MIBG-positive metastatic sites was associated with 84% and 74% local control, respectively. The number of MIBG-avid sites present after induction chemotherapy and surgery was predictive of progression-free and overall survival.

  5. Proton Radiotherapy for High-Risk Pediatric Neuroblastoma: Early Outcomes and Dose Comparison

    Energy Technology Data Exchange (ETDEWEB)

    Hattangadi, Jona A. [Harvard Radiation Oncology Program, Boston, MA (United States); Rombi, Barbara [Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA (United States); Provincial Agency for Proton Therapy, Trento (Italy); Yock, Torunn I.; Broussard, George [Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA (United States); Friedmann, Alison M.; Huang, Mary [Department of Pediatric Hematology-Oncology, Massachusetts General Hospital, Boston, MA (United States); Chen, Yen-Lin E.; Lu, Hsiao-Ming; Kooy, Hanne [Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA (United States); MacDonald, Shannon M., E-mail: smacdonald@partners.org [Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA (United States)

    2012-07-01

    Purpose: To report the early outcomes for children with high-risk neuroblastoma treated with proton radiotherapy (RT) and to compare the dose distributions for intensity-modulated photon RT (IMRT), three-dimensional conformal proton RT (3D-CPT), and intensity-modulated proton RT to the postoperative tumor bed. Methods and Materials: All patients with high-risk (International Neuroblastoma Staging System Stage III or IV) neuroblastoma treated between 2005 and 2010 at our institution were included. All patients received induction chemotherapy, surgical resection of residual disease, high-dose chemotherapy with stem cell rescue, and adjuvant 3D-CPT to the primary tumor sites. The patients were followed with clinical examinations, imaging, and laboratory testing every 6 months to monitor disease control and side effects. IMRT, 3D-CPT, and intensity-modulated proton RT plans were generated and compared for a representative case of adjuvant RT to the primary tumor bed followed by a boost. Results: Nine patients were treated with 3D-CPT. The median age at diagnosis was 2 years (range 10 months to 4 years), and all patients had Stage IV disease. All patients had unfavorable histologic characteristics (poorly differentiated histologic features in 8, N-Myc amplification in 6, and 1p/11q chromosomal abnormalities in 4). The median tumor size at diagnosis was 11.4 cm (range 7-16) in maximal dimension. At a median follow-up of 38 months (range 11-70), there were no local failures. Four patients developed distant failure, and, of these, two died of disease. Acute side effects included Grade 1 skin erythema in 5 patients and Grade 2 anorexia in 2 patients. Although comparable target coverage was achieved with all three modalities, proton therapy achieved substantial normal tissue sparing compared with IMRT. Intensity-modulated proton RT allowed additional sparing of the kidneys, lungs, and heart. Conclusions: Preliminary outcomes reveal excellent local control with proton therapy

  6. Heterogeneity of neuroblastoma cell identity defined by transcriptional circuitries.

    Science.gov (United States)

    Boeva, Valentina; Louis-Brennetot, Caroline; Peltier, Agathe; Durand, Simon; Pierre-Eugène, Cécile; Raynal, Virginie; Etchevers, Heather C; Thomas, Sophie; Lermine, Alban; Daudigeos-Dubus, Estelle; Geoerger, Birgit; Orth, Martin F; Grünewald, Thomas G P; Diaz, Elise; Ducos, Bertrand; Surdez, Didier; Carcaboso, Angel M; Medvedeva, Irina; Deller, Thomas; Combaret, Valérie; Lapouble, Eve; Pierron, Gaelle; Grossetête-Lalami, Sandrine; Baulande, Sylvain; Schleiermacher, Gudrun; Barillot, Emmanuel; Rohrer, Hermann; Delattre, Olivier; Janoueix-Lerosey, Isabelle

    2017-09-01

    Neuroblastoma is a tumor of the peripheral sympathetic nervous system, derived from multipotent neural crest cells (NCCs). To define core regulatory circuitries (CRCs) controlling the gene expression program of neuroblastoma, we established and analyzed the neuroblastoma super-enhancer landscape. We discovered three types of identity in neuroblastoma cell lines: a sympathetic noradrenergic identity, defined by a CRC module including the PHOX2B, HAND2 and GATA3 transcription factors (TFs); an NCC-like identity, driven by a CRC module containing AP-1 TFs; and a mixed type, further deconvoluted at the single-cell level. Treatment of the mixed type with chemotherapeutic agents resulted in enrichment of NCC-like cells. The noradrenergic module was validated by ChIP-seq. Functional studies demonstrated dependency of neuroblastoma with noradrenergic identity on PHOX2B, evocative of lineage addiction. Most neuroblastoma primary tumors express TFs from the noradrenergic and NCC-like modules. Our data demonstrate a previously unknown aspect of tumor heterogeneity relevant for neuroblastoma treatment strategies.

  7. High dose melphalan in the treatment of advanced neuroblastoma: results of a randomised trial (ENSG-1) by the European Neuroblastoma Study Group

    NARCIS (Netherlands)

    Pritchard, Jon; Cotterill, Simon J.; Germond, Shirley M.; Imeson, John; de Kraker, Jan; Jones, David R.

    2005-01-01

    High dose myeloablative chemotherapy ("megatherapy"), with haematopoietic stem cell support, is now widely used to consolidate response to induction chemotherapy in patients with advanced neuroblastoma. In this study (European Neuroblastoma Study Group, ENSG1), the value of melphalan myeloablative

  8. Seleno methionine-75 as a scanning agent for neuroblastoma

    International Nuclear Information System (INIS)

    Covington, E.E.; D'Angio, G.J.; Helson, L.; Romano, R.W.

    1974-01-01

    Neuroblastoma is a functioning tumor and patients with this tumor are known to excrete vanilmandelic acid and other degradation products of norepinephrine. It also accumulates and produces excess cystathionine for which methionine is a precursor in the normal anabolic pathway. This was the rationale for testing 75 Se-methionine as a possible scanning agent in patients with neuroblastoma. D'Angio et al reported the results of a preliminary investigation in which 3 of 4 patients with neuroblastoma, all with known metastases of the skull, had positive scans correctly localizing the disease. These preliminary data seemed encouraging, and further investigation was undertaken. The results are reported

  9. Localisation of beam offset jitter sources at ATF2

    CERN Document Server

    Pfingstner, J; Patecki, M; Schulte, D; Tomás, R

    2014-01-01

    For the commissioning and operation of modern particle accelerators, automated error detection and diagnostics methods are becoming increasingly important. In this paper, we present two such methods, which are capable of localising sources of beam offset jitter with a combination of correlation studies and so called degree of freedom plots. The methods were applied to the ATF2 beam line at KEK, where one of the major goals is the reduction of the beam offset jitter. Results of this localisation are shown in this paper. A big advantage of the presented method is its high robustness especially to varying optics parameters. Therefore, we believe that the developed beam offset jitter localisation methods can be easily applied to other accelerators.

  10. Differences in finger localisation performance of patients with finger agnosia.

    Science.gov (United States)

    Anema, Helen A; Kessels, Roy P C; de Haan, Edward H F; Kappelle, L Jaap; Leijten, Frans S; van Zandvoort, Martine J E; Dijkerman, H Chris

    2008-09-17

    Several neuropsychological studies have suggested parallel processing of somatosensory input when localising a tactile stimulus on one's own by pointing towards it (body schema) and when localising this touched location by pointing to it on a map of a hand (body image). Usually these reports describe patients with impaired detection, but intact sensorimotor localisation. This study examined three patients with a lesion of the angular gyrus with intact somatosensory processing, but with selectively disturbed finger identification (finger agnosia). These patients performed normally when pointing towards the touched finger on their own hand but failed to indicate this finger on a drawing of a hand or to name it. Similar defects in the perception of other body parts were not observed. The findings provide converging evidence for the dissociation between body image and body schema and, more importantly, reveal for the first time that this distinction is also present in higher-order cognitive processes selectively for the fingers.

  11. An ultrastructural and irradiation study of diffuse and localised kinetochore

    International Nuclear Information System (INIS)

    Bokhari, F.S.

    1979-05-01

    An electron microscope study of plant types Luzula nivea and Cyperus eragrostis with diffuse kinetochores and Crepis neglecta with localised kinetochore showed that Luzula has a rather different kinetochore organisation from Cyperus, with features approaching the localised type of Crepis. These studies included an examination of the ultrastructure of the kinetochore at metaphase at low magnification in control and irradiated material of Luzula; the chromosomal ultrastructure at high magnification at interphase and all stages of mitosis in Luzula, Cyperus and Crepis; and the ultrastructure of the nucleolus in Luzula, Cyperus and Crepis. Light microscopic studies were also performed showing the effects of irradiation on first mitotic division in Cyperus, Luzula and Crepis, mitotic aberrations in Cyperus and Crepis and meiosis in Cyperus. Finally, the survival with the diffuse as opposed to the localised kinetochore in M 1 and M 2 generations following seed irradiation was studied. (U.K.)

  12. Activity of iodine-123 metaiodobenzylguanidine in childhood neuroblastoma: lack of relation to tumour differentiation in vivo

    International Nuclear Information System (INIS)

    Brans, B.; Wiele, C. van de; Simons, M.; Dierckx, R.A.; Laureys, G.; Dhooge, C.; Schelfhout, V.; Potter, C.R. de

    1998-01-01

    Neuroblastoma (NB) tumour cells have a remarkable tendency to differentiate spontaneously or under the influence of certain drugs. It is not clear whether metaiodobenzylguanidine (MIBG) uptake correlates with differentiation of NB cells. In 28 tumours of 26 patients, iodine-123 MIBG uptake in primary NBs was studied in relation to tumour differentiation, tumour size, cell density and degree of necrosis in subsequently resected specimens. Genetic features such as the presence of chromosomal aberrations (1p-deletion and MYCN amplification) and/or P-glycoprotein (mdr-1 gene product) were also evaluated in relation to MIBG uptake. A highly variable and unpredictable intensity of MIBG uptake was observed in primary as well as secondary resected tumours. This intensity did not relate to any of the above-mentioned factors except that there was a trend towards more intense uptake with increasing size of the tumour. We conclude from our observations that, in contrast to commonly held opinion, well-differentiated tumours do not a priori show a lower MIBG uptake in vivo, even when there are a low number of viable cells and a high degree of necrosis. The degree of differentiation or tumour viability and necrosis following longstanding chemotherapeutic treatment cannot be predicted by the MIBG scan findings. The observed MIBG uptake may be importantly influenced by factors other than those associated with cellular differentiation. (orig.)

  13. Activity of iodine-123 metaiodobenzylguanidine in childhood neuroblastoma: lack of relation to tumour differentiation in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Brans, B.; Wiele, C. van de; Simons, M.; Dierckx, R.A. [Division of Nuclear Medicine, University Hospital Gent, Gent (Belgium); Laureys, G.; Dhooge, C. [Department of Pediatric Hemato-oncology, University Hospital Gent, Gent (Belgium); Schelfhout, V.; Potter, C.R. de [Department of Pathology, University Hospital Gent, Gent (Belgium)

    1998-02-01

    Neuroblastoma (NB) tumour cells have a remarkable tendency to differentiate spontaneously or under the influence of certain drugs. It is not clear whether metaiodobenzylguanidine (MIBG) uptake correlates with differentiation of NB cells. In 28 tumours of 26 patients, iodine-123 MIBG uptake in primary NBs was studied in relation to tumour differentiation, tumour size, cell density and degree of necrosis in subsequently resected specimens. Genetic features such as the presence of chromosomal aberrations (1p-deletion and MYCN amplification) and/or P-glycoprotein (mdr-1 gene product) were also evaluated in relation to MIBG uptake. A highly variable and unpredictable intensity of MIBG uptake was observed in primary as well as secondary resected tumours. This intensity did not relate to any of the above-mentioned factors except that there was a trend towards more intense uptake with increasing size of the tumour. We conclude from our observations that, in contrast to commonly held opinion, well-differentiated tumours do not a priori show a lower MIBG uptake in vivo, even when there are a low number of viable cells and a high degree of necrosis. The degree of differentiation or tumour viability and necrosis following longstanding chemotherapeutic treatment cannot be predicted by the MIBG scan findings. The observed MIBG uptake may be importantly influenced by factors other than those associated with cellular differentiation. (orig.) With 2 figs., 1 tab., 19 refs.

  14. Monitoring corrosion rates and localised corrosion in low conductivity water

    DEFF Research Database (Denmark)

    Hilbert, Lisbeth Rischel

    2006-01-01

    Monitoring of low corrosion rates and localised corrosion in a media with low conductivity is a challenge. In municipal district heating, quality control may be improved by implementing on-line corrosion monitoring if a suitable technique can be identified to measure both uniform and localised...... corrosion. Electrochemical techniques (LPR, EIS, crevice corrosion current) as well as direct measurement techniques (high-sensitive electrical resistance, weight loss) have been applied in operating plants. Changes in the corrosion processes are best monitored in non-aggressive, low conductivity media...

  15. Experimental investigation of edge localised modes in JET

    International Nuclear Information System (INIS)

    Lindholm Colton, A.

    1993-08-01

    Edge Localised Modes (ELMs) in the JET tokamak have been studied experimentally, using density profile and fluctuation data from a multichannel reflectometer and temperature profile data from an ECE heterodyne radiometer. The following topics have been investigated: The radial extent and localisation of the density and temperature profile perturbations caused by the ELMs. Fluctuations in the density and magnetic field in connection with the ELMs. The correlation between the repetition frequency of the L-H transition ELMs, and the plasma edge temperature and density. Trajectories in n-T space prior to ELMs later in the H-mode. (au) (39 refs.)

  16. CASE REPORT Proptosis as a manifestation of neuroblastoma ...

    African Journals Online (AJOL)

    in children less than 15 years of age, with 90% of all neuroblastomas occurring before ... Examination of the eyes showed a left axial, non-pulsatile proptosis with full ... robulbar enhancing masses (white arrows) with sphenoid bone involve-.

  17. Hepatic imaging in stage IV-S neuroblastoma

    International Nuclear Information System (INIS)

    Franken, E.A. Jr.; Smith, W.L.; Iowa Univ., Iowa City; Cohen, M.D.; Kisker, C.T.; Platz, C.E.

    1986-01-01

    Stage IV-S neuroblastoma describes a group of infants with tumor spread limited to liver, skin, or bone marrow. Such patients, who constitute about 25% of affected infants with neuroblastoma, may expect spontaneous tumor remission. We report 18 infants with Stage IV-S neuroblastoma, 83% of whom had liver involvement. Imaging investigations included Technetium 99m sulfur colloid scan, ultrasound, and CT. Two patterns of liver metastasis were noted: ill-defined nodules or diffuse tumor throughout the liver. Distinction of normal and abnormal liver with diffuse type metastasis could be quite difficult, particularly with liver scans. We conclude that patients with Stage IV-S neuroblastoma have ultrasound or CT examination as an initial workup, with nuclear medicine scans reserved for followup studies. (orig.)

  18. Intraoperative Localisation of Impalpable Breast Lesions Utilising the ROLLIS Technique Following Peritumoral 99mTc-colloid Sentinel Node Lymphoscintigraphy.

    Science.gov (United States)

    Hung, Te-Jui; Burrage, John; Bourke, Anita; Taylor, Donna

    2017-08-24

    Ultrasound or stereotactic guided hook-wire localisation has been the standard-of-care for the pre-surgical localisation of impalpable breast lesions, which account for approximately a third of all breast cancer. Radioguided occult lesion localisation using I-125 seeds (ROLLIS) is a relatively new technique for guiding surgical excision of impalpable breast lesions, and is a promising alternative to the traditional hook-wire method. When combined with Tc-99m labelled colloid for sentinel node mapping in clinically indicated cases, there has been uncertainty regarding whether the downscatter of Tc-99m into the I-125 energy spectrum could adversely affect the intra-operative detection of the I-125 seed, especially pertaining to a peritumoral injection. To evaluate the percentage contribution of downscattered activity from Tc-99m into the I-125 energy spectrum in simulated intra-operative resections of an I-125 seed following different sentinel node injection techniques. Two scenarios were simulated using breast phantoms with lean chicken breast. The first scenario, with a 2cm distance between the Tc-99m injection site and the I-125 seed, simulated a periareolar ipsiquadrant injection with the subdermal or intradermal technique. The second scenario simulated a peritumoral injection technique with the Tc-99m bolus and an I-125 seed at the same site. Count rates were acquired with a hand-held gamma probe, and the percentage contribution of downscattered Tc-99m gamma photons to the I-125 energy window was calculated. In scenarios one and two, downscattered Tc-99m activity contributed 0.5% and 33% respectively to the detected count rate in the I-125 energy window. In both scenarios, the I-125 seed was successfully localised and removed using the gamma probe. There is no significant contribution of downscattered activity associated with a peritumoral injection of Tc-99m to adversely affect the accurate intra-operative localisation of an I- 125 seed. Copyright© Bentham

  19. Neuroblastoma: morphological pattern, molecular genetic features, and prognostic factors

    Directory of Open Access Journals (Sweden)

    A. M. Stroganova

    2016-01-01

    Full Text Available Neuroblastoma, the most common extracranial tumor of childhood, arises from the developing neurons of the sympathetic nervous system (neural cress stem cells and has various biological and clinical characteristics. The mean age at disease onset is 18 months. Neuroblastoma has a number of unique characteristics: a capacity for spontaneous regression in babies younger than 12 months even in the presence of distant metastases, for differentiation (maturation into ganglioneuroma in infants after the first year of life, and for swift aggressive development and rapid metastasis. There are 2 clinical classifications of neuroblastoma: the International neuroblastoma staging system that is based on surgical results and the International Neuroblastoma Risk Group Staging System. One of the fundamentally important problems for the clinical picture of neuroblastoma is difficulties making its prognosis. Along with clinical parameters (a patient’s age, tumor extent and site, some histological, molecular biochemical (ploidy and genetic (chromosomal aberrations, MYCN gene status, deletion of the locus 1p36 and 11q, the longer arm of chromosome 17, etc. characteristics of tumor cells are of considerable promise. MYCN gene amplification is observed in 20–30 % of primary neuroblastomas and it is one of the major indicators of disease aggressiveness, early chemotherapy resistance, and a poor prognosis. There are 2 types of MYCN gene amplification: extrachromosomal (double acentric chromosomes and intrachromosomal (homogenically painted regions. Examination of double acentric chromosomes revealed an interesting fact that it may be eliminated (removed from the nucleus through the formation of micronuclei. MYCN oncogene amplification is accompanied frequently by 1p36 locus deletion and longer 17q arm and less frequently by 11q23 deletion; these are poor prognostic factors for the disease. The paper considers in detail the specific, unique characteristics of the

  20. Treatment and outcome of adult-onset neuroblastoma.

    Science.gov (United States)

    Suzuki, Maya; Kushner, Brian H; Kramer, Kim; Basu, Ellen M; Roberts, Stephen S; Hammond, William J; LaQuaglia, Michael P; Wolden, Suzanne L; Cheung, Nai-Kong V; Modak, Shakeel

    2018-03-25

    Adult-onset neuroblastoma is rare and little is known about its biology and clinical course. There is no established therapy for adult-onset neuroblastoma. Anti-GD2 immunotherapy is now standard therapy in children with high-risk neuroblastoma; however, its use has not been reported in adults. Forty-four adults (18-71 years old) diagnosed with neuroblastoma between 1979 and 2015 were treated at Memorial Sloan Kettering Cancer Center. Five, 1, 5 and 33 patients had INSS stage 1, 2, 3 and 4 diseases, respectively. Genetic abnormalities included somatic ATRX (58%) and ALK mutations (42%) but not MYCN-amplification. In the 11 patients with locoregional disease, 10-year progression-free (PFS) and overall survival (OS) was 35.4 ± 16.1% and 61.4 ± 15.3%, respectively. Among 33 adults with stage 4 neuroblastoma, 7 (21%) achieved complete response (CR) after induction chemotherapy and/or surgery. Seven patients with primary refractory neuroblastoma (all with osteomedullary but no soft tissue disease) received anti-GD2 antibodies, mouse or humanized 3F8. Antibody-related adverse events were similar to those in children, response rate being 71.4%. In patients with stage 4 disease at diagnosis, 5-year PFS was 9.7± 5.3% and most patients who were alive with disease at 5 years died of neuroblastoma over the next 5 years, 10-year OS being only 19.0 ± 8.2%. Patients who achieved CR after induction had superior PFS and OS (p = 0.006, p = 0.031, respectively). Adult-onset neuroblastoma appeared to have different biology from pediatric or adolescent NB, and poorer outcome. Complete disease control appeared to improve long-term survival. Anti-GD2 immunotherapy was well tolerated and might be beneficial. © 2018 UICC.

  1. Upregulation of LYAR induces neuroblastoma cell proliferation and survival.

    Science.gov (United States)

    Sun, Yuting; Atmadibrata, Bernard; Yu, Denise; Wong, Matthew; Liu, Bing; Ho, Nicholas; Ling, Dora; Tee, Andrew E; Wang, Jenny; Mungrue, Imran N; Liu, Pei Y; Liu, Tao

    2017-09-01

    The N-Myc oncoprotein induces neuroblastoma by regulating gene transcription and consequently causing cell proliferation. Paradoxically, N-Myc is well known to induce apoptosis by upregulating pro-apoptosis genes, and it is not clear how N-Myc overexpressing neuroblastoma cells escape N-Myc-mediated apoptosis. The nuclear zinc finger protein LYAR has recently been shown to modulate gene expression by forming a protein complex with the protein arginine methyltransferase PRMT5. Here we showed that N-Myc upregulated LYAR gene expression by binding to its gene promoter. Genome-wide differential gene expression studies revealed that knocking down LYAR considerably upregulated the expression of oxidative stress genes including CHAC1, which depletes intracellular glutathione and induces oxidative stress. Although knocking down LYAR expression with siRNAs induced oxidative stress, neuroblastoma cell growth inhibition and apoptosis, co-treatment with the glutathione supplement N-acetyl-l-cysteine or co-transfection with CHAC1 siRNAs blocked the effect of LYAR siRNAs. Importantly, high levels of LYAR gene expression in human neuroblastoma tissues predicted poor event-free and overall survival in neuroblastoma patients, independent of the best current markers for poor prognosis. Taken together, our data suggest that LYAR induces proliferation and promotes survival of neuroblastoma cells by repressing the expression of oxidative stress genes such as CHAC1 and suppressing oxidative stress, and identify LYAR as a novel co-factor in N-Myc oncogenesis.

  2. /sup 131/I-meta-iodobenzylguanidine scintigraphy of neuroblastomas

    International Nuclear Information System (INIS)

    Munkner, T.

    1986-01-01

    Sixteen neuroblastoma patients have been studied by /sup 131/I-meta-iodobenzylguanidine scintigraphy. Three patients were possibly cured, and their scintigraphy results were normal. Thirteen patients had tumors and metastases demonstrated by /sup 131/I-MIBG, two of these patients had a normal vanillylmandelic acid excretion levels. One patient has been treated by /sup 131/I-MIBG, but died. /sup 131/I-MIBG was concentrated in other cells too, e.g., in erythrocytes and platelets. Neuroblastoma is the most common solid malignant disease in children. It has a poor prognosis in patients more than one year old. Early detection and a display of the spread of the tumor is of utmost importance for planning and controlling the treatment. Mass screening for neuroblastoma in infants has been suggested and tried in Japan. Scintigraphy after injection of /sup 131/I-meta-iodobenzylguanidine has been used successfully for locating neuroblastomas. An initial study failed to demonstrate neuroblastoma by means of MIBG in two patients. Since the latter part of 1983, MIBG has been used in a number of European centers for imaging neuroblastomas with very promising results, and a multicenter investigation has been initiated. The Ann Arbor group has recently extended its studies to a group of ten patients and has confirmed the European results

  3. Natural killer cells facilitate PRAME-specific T-cell reactivity against neuroblastoma

    Science.gov (United States)

    Spel, Lotte; Boelens, Jaap-Jan; van der Steen, Dirk M.; Blokland, Nina J.G.; van Noesel, Max M.; Molenaar, Jan J.; Heemskerk, Mirjam H.M.

    2015-01-01

    Neuroblastoma is the most common solid tumor in children with an estimated 5-year progression free survival of 20–40% in stage 4 disease. Neuroblastoma actively avoids recognition by natural killer (NK) cells and cytotoxic T lymphocytes (CTLs). Although immunotherapy has gained traction for neuroblastoma treatment, these immune escape mechanisms restrain clinical results. Therefore, we aimed to improve neuroblastoma immunogenicity to further the development of antigen-specific immunotherapy against neuroblastoma. We found that neuroblastoma cells significantly increase surface expression of MHC I upon exposure to active NK cells which thereby readily sensitize neuroblastoma cells for recognition by CTLs. We show that oncoprotein PRAME serves as an immunodominant antigen for neuroblastoma as NK-modulated neuroblastoma cells are recognized by PRAMESLLQHLIGL/A2-specific CTL clones. Furthermore, NK cells induce MHC I upregulation in neuroblastoma through contact-dependent secretion of IFNγ. Our results demonstrate remarkable plasticity in the peptide/MHC I surface expression of neuroblastoma cells, which is reversed when neuroblastoma cells experience innate immune attack by sensitized NK cells. These findings support the exploration of NK cells as adjuvant therapy to enforce neuroblastoma-specific CTL responses. PMID:26452036

  4. Olfactory neuroblastoma complicated by postirradiation pneumocephalus

    Energy Technology Data Exchange (ETDEWEB)

    Fusejima, Toru; Matsumura, Kenichirou; Hayano, Makoto [Mito Saiseikai Hospital (Japan)

    1990-11-01

    A 56-year-old male was admitted with the complaints of nasal bleeding, gait disturbance, and disturbance of consciousness. Neurological examination revealed drowsiness, right hemiparesis, and choked discs. Computed tomography scan showed an enhanced mass at the frontal base, which extended to the left nasal and paranasal cavities. Angiography showed a tumor stain with a mass sign. The intracranial part of the tumor was removed completely and he was discharged ambulatorily. Two months after surgery, however, he was admitted again for the regrowth of the tumor. Ventriculoperitoneal shunting was emplaced and radiation therapy was given to the brain and nasal cavity. After 3000 rad irradiation the clinical condition suddenly became worse because of pneumocephalus. The cranial tumor disappeared after irradiation but he died of metastases and general prostration. Clinically this case was diagnosed as an olfactory groove meningioma at first, but immunohistochemical diagnosis was olfactory neuroblastoma. (author).

  5. Mesenchymal change and drug resistance in neuroblastoma.

    Science.gov (United States)

    Naiditch, Jessica A; Jie, Chunfa; Lautz, Timothy B; Yu, Songtao; Clark, Sandra; Voronov, Dimitry; Chu, Fei; Madonna, Mary Beth

    2015-01-01

    Metastatic initiation has many phenotypic similarities to epithelial-to-mesenchymal transition, including loss of cell-cell adhesion, increased invasiveness, and increased cell mobility. We have previously demonstrated that drug resistance is associated with a metastatic phenotype in neuroblastoma (NB). The purpose of this project was to determine if the development of doxorubicin resistance is associated with characteristics of mesenchymal change in human NB cells. Total RNA was isolated from wild type (WT) and doxorubicin-resistant (DoxR) human NB cell lines (SK-N-SH and SK-N-BE(2)C) and analyzed using the Illumina Human HT-12 version 4 Expression BeadChip. Differentially expressed genes (DEGs) were identified. Volcano plots and heat maps were generated. Genes of interest with a fold change in expression >1.5 and an adjusted P change via multiple pathways in the transition to a drug-resistant state. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. [Endoscopic full-thickness resection].

    Science.gov (United States)

    Meier, B; Schmidt, A; Caca, K

    2016-08-01

    Conventional endoscopic resection techniques such as endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) are powerful tools for the treatment of gastrointestinal (GI) neoplasms. However, those techniques are limited to the superficial layers of the GI wall (mucosa and submucosa). Lesions without lifting sign (usually arising from deeper layers) or lesions in difficult anatomic positions (appendix, diverticulum) are difficult - if not impossible - to resect using conventional techniques, due to the increased risk of complications. For larger lesions (>2 cm), ESD appears to be superior to the conventional techniques because of the en bloc resection, but the procedure is technically challenging, time consuming, and associated with complications even in experienced hands. Since the development of the over-the-scope clips (OTSC), complications like bleeding or perforation can be endoscopically better managed. In recent years, different endoscopic full-thickness resection techniques came to the focus of interventional endoscopy. Since September 2014, the full-thickness resection device (FTRD) has the CE marking in Europe for full-thickness resection in the lower GI tract. Technically the device is based on the OTSC system and combines OTSC application and snare polypectomy in one step. This study shows all full-thickness resection techniques currently available, but clearly focuses on the experience with the FTRD in the lower GI tract.

  7. Time Localisation of Surface Defects on Optical Discs

    DEFF Research Database (Denmark)

    Odgaard, Peter Fogh; Wickerhauser, M.V.

    Many have experienced problems with their Compact Disc player when a disc with a scratch or a finger print is tried played. One way to improve the playability of discs with such a defect, is to locate the defect in time and then handle it in a special way. As a consequence this time localisation...

  8. Immunogold staining procedure for the localisation of regulatory peptides.

    Science.gov (United States)

    Varndell, I M; Tapia, F J; Probert, L; Buchan, A M; Gu, J; De Mey, J; Bloom, S R; Polak, J M

    1982-01-01

    The use of protein A- and IgG-conjugated colloidal gold staining methods for the immuno-localisation of peptide hormones and neurotransmitters at light- and electron microscope level are described and discussed. Bright-field and dark-ground illumination modes have been used to visualise the gold-labelled antigenic sites at the light microscope level. Immunogold staining procedures at the ultrastructural level using region-specific antisera have been adopted to localise specific molecular forms of peptides including gastrin (G17 and G34), glucagon and pro-glucagon, insulin and pro-insulin, in normal tissue and in tumours of the gastroenteropancreatic system. Similar methods have been used to demonstrate the heterogeneity of p-type nerves in the enteric nervous system. Vasoactive intestinal polypeptide (VIP) has been localised to granular sites (mean +/- S.D. granule diameter = 98 +/- 19 nm) in nerve terminals of the enteric plexuses and in tumour cells of diarrhoeogenic VIP-producing neoplasias (mean +/- S.D. granule diameter = 126 +/- 37 nm) using immunogold procedures applied to ultraviolet-cured ultrathin sections. Co-localisation of amines and peptides in carotid body type I cells and in chromaffin cells of normal adrenal medulla and phaeochromocytomas has also been demonstrated. Advantages of the immunogold procedures over alternative immunocytochemical techniques are discussed.

  9. Human SLAM, indoor localisation of devices and users

    NARCIS (Netherlands)

    Bulten, W.; Rossum, A.C. van; Haselager, W.F.G.; Guerrero, J.E.

    2016-01-01

    The indoor localisation problem is more complex than just finding whereabouts of users. Finding positions of users relative to the devices of a smart space is even more important. Unfortunately, configuring such systems manually is a tedious process, requires expert knowledge, and is sensitive to

  10. Cutting Edge Localisation in an Edge Profile Milling Head

    NARCIS (Netherlands)

    Fernandez Robles, Laura; Azzopardi, George; Alegre, Enrique; Petkov, Nicolai

    2015-01-01

    Wear evaluation of cutting tools is a key issue for prolonging their lifetime and ensuring high quality of products. In this paper, we present a method for the effective localisation of cutting edges of inserts in digital images of an edge profile milling head. We introduce a new image data set of

  11. Radioactive probes for human gene localisation by in situ hybridisation

    International Nuclear Information System (INIS)

    Fennell, S.J.

    1980-07-01

    Radioactive probes of high specific activity have been used for human gene localisation on metaphase chromosome preparations. Human 5S ribosomal RNA was used as a model system, as a probe for the localisation of human 5S ribosomal genes. 125 I-labelled mouse 5S ribosomal RNA was used to study the 5S ribosomal gene content and arrangement in families with translocations on the long arm of chromosome 1 close to or containing the 5S ribosomal RNA locus, by in situ hybridisation to human metaphase chromosomes from peripheral blood cultures. This confirmed the chromosomal assignment of 5S ribosomal genes to 1q 42-43. In situ hybridisation probes were also prepared from recombinant plasmids containing Xenopus laevis oocyte 5S or 28S/18S gene sequences to give [ 3 H]-labelled cRNA and [ 3 H]-labelled nick-translated plasmid DNA. Studies on the kinetics of hybridisation of plasmid probes with and without ribosomal gene sequences questioned the role of plasmid DNA for amplification of signal during gene localisation. Gene localisation was obtained with nick-translated plasmid DNA containing the 28S/18S ribosomal DNA insert after short exposure times, but poor results were obtained using a [ 3 H]-labelled cRNA probe transcribed from the plasmid with the 5S gene insert. (author)

  12. Application of the Localisation Platform Crowdin in Translator Education

    Science.gov (United States)

    Kudla, Dominik

    2017-01-01

    This article is an attempt to briefly describe the potential of the online localisation platform Crowdin for the education of the future translators at universities and in private courses or workshops. This description is provided on the basis of the information gathered through the user experience of the author and uses the example of the Khan…

  13. Scanning Kelvin Probe applied to localised corrosion | Haque ...

    African Journals Online (AJOL)

    This paper focuses on specific applications of the SKP system. The instrument is calibrated, using different thickness of a model polymer Poly Vinyl Butyral (PVB) on mild steel and on galvanised steel. Artificial defects are used to show how the instrument is capable of detecting a localised corrosion cell and its ability to ...

  14. Proton-Beam Therapy for Olfactory Neuroblastoma

    International Nuclear Information System (INIS)

    Nishimura, Hideki; Ogino, Takashi; Kawashima, Mitsuhiko; Nihei, Keiji; Arahira, Satoko; Onozawa, Masakatsu; Katsuta, Shoichi; Nishio, Teiji

    2007-01-01

    Purpose: To analyze the feasibility and efficacy of proton-beam therapy (PBT) for olfactory neuroblastoma (ONB) as a definitive treatment, by reviewing our preliminary experience. Olfactory neuroblastoma is a rare disease, and a standard treatment strategy has not been established. Radiation therapy for ONB is challenging because of the proximity of ONBs to critical organs. Proton-beam therapy can provide better dose distribution compared with X-ray irradiation because of its physical characteristics, and is deemed to be a feasible treatment modality. Methods and Materials: A retrospective review was performed on 14 patients who underwent PBT for ONB as definitive treatment at the National Cancer Center Hospital East (Kashiwa, Chiba, Japan) from November 1999 to February 2005. A total dose of PBT was 65 cobalt Gray equivalents (Gy E ), with 2.5-Gy E once-daily fractionations. Results: The median follow-up period for surviving patients was 40 months. One patient died from disseminated disease. There were two persistent diseases, one of which was successfully salvaged with surgery. The 5-year overall survival rate was 93%, the 5-year local progression-free survival rate was 84%, and the 5-year relapse-free survival rate was 71%. Liquorrhea was observed in one patient with Kadish's stage C disease (widely destroying the skull base). Most patients experienced Grade 1 to 2 dermatitis in the acute phase. No other adverse events of Grade 3 or greater were observed according to the RTOG/EORTC acute and late morbidity scoring system. Conclusions: Our preliminary results of PBT for ONB achieved excellent local control and survival outcomes without serious adverse effects. Proton-beam therapy is considered a safe and effective modality that warrants further study

  15. Endoscopic resection of subepithelial tumors.

    Science.gov (United States)

    Schmidt, Arthur; Bauder, Markus; Riecken, Bettina; Caca, Karel

    2014-12-16

    Management of subepithelial tumors (SETs) remains challenging. Endoscopic ultrasound (EUS) has improved differential diagnosis of these tumors but a definitive diagnosis on EUS findings alone can be achieved in the minority of cases. Complete endoscopic resection may provide a reasonable approach for tissue acquisition and may also be therapeutic in case of malignant lesions. Small SET restricted to the submucosa can be removed with established basic resection techniques. However, resection of SET arising from deeper layers of the gastrointestinal wall requires advanced endoscopic methods and harbours the risk of perforation. Innovative techniques such as submucosal tunneling and full thickness resection have expanded the frontiers of endoscopic therapy in the past years. This review will give an overview about endoscopic resection techniques of SET with a focus on novel methods.

  16. Approach to sensor node calibration for efficient localisation in wireless sensor networks in realistic scenarios

    CSIR Research Space (South Africa)

    Mwila, MK

    2014-06-01

    Full Text Available Localisation or position determination is one of the most important applications for the wireless sensor networks. Numerous current techniques for localisation of sensor nodes use the Received Signal Strength Indicator (RSSI) from sensor nodes...

  17. Learning endoscopic resection in the esophagus

    NARCIS (Netherlands)

    van Vilsteren, Frederike G. I.; Pouw, Roos E.; Herrero, Lorenza Alvarez; Bisschops, Raf; Houben, Martin; Peters, Frans T. M.; Schenk, B. E.; Weusten, Bas L. A. M.; Schoon, Erik J.; Bergman, Jacques J. G. H. M.

    Background: Endoscopic resection is the cornerstone of endoscopic management of esophageal early neoplasia. However, endoscopic resection is a complex technique requiring knowledge and expertise. Our aims were to identify the most important learning points in performing endoscopic resection in a

  18. [Laparoscopic liver resection: lessons learned after 132 resections].

    Science.gov (United States)

    Robles Campos, Ricardo; Marín Hernández, Caridad; Lopez-Conesa, Asunción; Olivares Ripoll, Vicente; Paredes Quiles, Miriam; Parrilla Paricio, Pascual

    2013-10-01

    After 20 years of experience in laparoscopic liver surgery there is still no clear definition of the best approach (totally laparoscopic [TLS] or hand-assisted [HAS]), the indications for surgery, position, instrumentation, immediate and long-term postoperative results, etc. To report our experience in laparoscopic liver resections (LLRs). Over a period of 10 years we performed 132 LLRs in 129 patients: 112 malignant tumours (90 hepatic metastases; 22 primary malignant tumours) and 20 benign lesions (18 benign tumours; 2 hydatid cysts). Twenty-eight cases received TLS and 104 had HAS. 6 right hepatectomies (2 as the second stage of a two-stage liver resection); 6 left hepatectomies; 9 resections of 3 segments; 42 resections of 2 segments; 64 resections of one segment; and 5 cases of local resections. There was no perioperative mortality, and morbidity was 3%. With TLS the resection was completed in 23/28 cases, whereas with HAS it was completed in all 104 cases. Transfusion: 4,5%; operating time: 150min; and mean length of stay: 3,5 days. The 1-, 3- and 5-year survival rates for the primary malignant tumours were 100, 86 and 62%, and for colorectal metastases 92, 82 and 52%, respectively. LLR via both TLS and HAS in selected cases are similar to the results of open surgery (similar 5-year morbidity, mortality and survival rates) but with the advantages of minimally invasive surgery. Copyright © 2012 AEC. Published by Elsevier Espana. All rights reserved.

  19. Mutations in PIK3CA are infrequent in neuroblastoma

    International Nuclear Information System (INIS)

    Dam, Vincent; Morgan, Brian T; Mazanek, Pavel; Hogarty, Michael D

    2006-01-01

    Neuroblastoma is a frequently lethal pediatric cancer in which MYCN genomic amplification is highly correlated with aggressive disease. Deregulated MYC genes require co-operative lesions to foster tumourigenesis and both direct and indirect evidence support activated Ras signaling for this purpose in many cancers. Yet Ras genes and Braf, while often activated in cancer cells, are infrequent targets for activation in neuroblastoma. Recently, the Ras effector PIK3CA was shown to be activated in diverse human cancers. We therefore assessed PIK3CA for mutation in human neuroblastomas, as well as in neuroblastomas arising in transgenic mice with MYCN overexpressed in neural-crest tissues. In this murine model we additionally surveyed for Ras family and Braf mutations as these have not been previously reported. Sixty-nine human neuroblastomas (42 primary tumors and 27 cell lines) were sequenced for PIK3CA activating mutations within the C2, helical and kinase domain 'hot spots' where 80% of mutations cluster. Constitutional DNA was sequenced in cases with confirmed alterations to assess for germline or somatic acquisition. Additionally, Ras family members (Hras1, Kras2 and Nras) and the downstream effectors Pik3ca and Braf, were sequenced from twenty-five neuroblastomas arising in neuroblastoma-prone transgenic mice. We identified mutations in the PIK3CA gene in 2 of 69 human neuroblastomas (2.9%). Neither mutation (R524M and E982D) has been studied to date for effects on lipid kinase activity. Though both occurred in tumors with MYCN amplification the overall rate of PIK3CA mutations in MYCN amplified and single-copy tumors did not differ appreciably (2 of 31 versus 0 of 38, respectively). Further, no activating mutations were identified in a survey of Ras signal transduction genes (including Hras1, Kras2, Nras, Pik3ca, or Braf genes) in twenty-five neuroblastic tumors arising in the MYCN-initiated transgenic mouse model. These data suggest that activating

  20. Germ plasm localisation of the HELICc of Vasa in Drosophila: analysis of domain sufficiency and amino acids critical for localisation

    Science.gov (United States)

    Wang, Szu-Chieh; Hsu, Hao-Jen; Lin, Gee-Way; Wang, Ting-Fang; Chang, Chun-Che; Lin, Ming-Der

    2015-09-01

    Formation of the germ plasm drives germline specification in Drosophila and some other insects such as aphids. Identification of the DEAD-box protein Vasa (Vas) as a conserved germline marker in flies and aphids suggests that they share common components for assembling the germ plasm. However, to which extent the assembly order is conserved and the correlation between functions and sequences of Vas remain unclear. Ectopic expression of the pea aphid Vas (ApVas1) in Drosophila did not drive its localisation to the germ plasm, but ApVas1 with a replaced C-terminal domain (HELICc) of Drosophila Vas (DmVas) became germ-plasm restricted. We found that HELICc itself, through the interaction with Oskar (Osk), was sufficient for germ-plasm localisation. Similarly, HELICc of the grasshopper Vas could be recruited to the germ plasm in Drosophila. Nonetheless, germ-plasm localisation was not seen in the Drosophila oocytes expressing HELICcs of Vas orthologues from aphids, crickets, and mice. We further identified that glutamine (Gln) 527 within HELICc of DmVas was critical for localisation, and its corresponding residue could also be detected in grasshopper Vas yet missing in the other three species. This suggests that Gln527 is a direct target of Osk or critical to the maintenance of HELICc conformation.

  1. Stage IVN neuroblastoma: MRI diagnosis of left supraclavicular ''Virchow's'' nodal spread

    International Nuclear Information System (INIS)

    Abramson, S.J.; Berdon, W.E.; Stolar, C.; Ruzal-Shapiro, C.; Garvin, J.

    1996-01-01

    Stage IV neuroblastoma is associated with high mortality; an exception are patients whose stage IV status includes distant positive nodes, but no skeletal metastases - stage IVN neuroblastoma. We describe our experience with preoperative MRI in three patients with extensive abdominal neuroblastoma without cortical bony involvement but with unsuspected metastatic involvement to the left supraclavicular (Virchow's) node. We review findings of left supraclavicular nodal spread in five earlier cases of IVN neuroblastoma. (orig.). With 3 figs., 1 tab

  2. Silencing Intersectin 1 Slows Orthotopic Neuroblastoma Growth in Mice.

    Science.gov (United States)

    Harris, Jamie; Herrero-Garcia, Erika; Russo, Angela; Kajdacsy-Balla, Andre; O'Bryan, John P; Chiu, Bill

    2017-11-01

    Neuroblastoma accounts for 15% of all pediatric cancer deaths. Intersectin 1 (ITSN1), a scaffold protein involved in phosphoinositide 3-kinase (PI3K) signaling, regulates neuroblastoma cells independent of MYCN status. We hypothesize that by silencing ITSN1 in neuroblastoma cells, tumor growth will be decreased in an orthotopic mouse tumor model. SK-N-AS neuroblastoma cells transfected with empty vector (pSR), vectors expressing scrambled shRNA (pSCR), or shRNAs targeting ITSN1 (sh#1 and sh#2) were used to create orthotopic neuroblastoma tumors in mice. Volume was monitored weekly with ultrasound. End-point was tumor volume >1000 mm. Tumor cell lysates were analyzed with anti-ITSN1 antibody by Western blot. Orthotopic tumors were created in all cell lines. Twenty-five days post injection, pSR tumor size was 917.6±247.7 mm, pSCR was 1180±159.9 mm, sh#1 was 526.3±212.8 mm, and sh#2 was 589.2±74.91 mm. sh#1-tumors and sh#2-tumors were smaller than pSCR (P=0.02), no difference between sh#1 and sh#2. Survival was superior in sh#2-tumors (P=0.02), trended towards improved survival in sh#1-tumors (P=0.09), compared with pSCR-tumors, no difference in pSR tumors. Western blot showed decreased ITSN1 expression in sh#1 and sh#2 compared with pSR and pSCR. Silencing ITSN1 in neuroblastoma cells led to decreased tumor growth in an orthotopic mouse model. Orthotopic animal models can provide insight into the role of ITSN1 pathways in neuroblastoma tumorigenesis.

  3. Telomerase activation by genomic rearrangements in high-risk neuroblastoma

    Science.gov (United States)

    Peifer, Martin; Hertwig, Falk; Roels, Frederik; Dreidax, Daniel; Gartlgruber, Moritz; Menon, Roopika; Krämer, Andrea; Roncaioli, Justin L.; Sand, Frederik; Heuckmann, Johannes M.; Ikram, Fakhera; Schmidt, Rene; Ackermann, Sandra; Engesser, Anne; Kahlert, Yvonne; Vogel, Wenzel; Altmüller, Janine; Nürnberg, Peter; Thierry-Mieg, Jean; Thierry-Mieg, Danielle; Mariappan, Aruljothi; Heynck, Stefanie; Mariotti, Erika; Henrich, Kai-Oliver; Glöckner, Christian; Bosco, Graziella; Leuschner, Ivo; Schweiger, Michal R.; Savelyeva, Larissa; Watkins, Simon C.; Shao, Chunxuan; Bell, Emma; Höfer, Thomas; Achter, Viktor; Lang, Ulrich; Theissen, Jessica; Volland, Ruth; Saadati, Maral; Eggert, Angelika; de Wilde, Bram; Berthold, Frank; Peng, Zhiyu; Zhao, Chen; Shi, Leming; Ortmann, Monika; Büttner, Reinhard; Perner, Sven; Hero, Barbara; Schramm, Alexander; Schulte, Johannes H.; Herrmann, Carl; O’Sullivan, Roderick J.; Westermann, Frank; Thomas, Roman K.; Fischer, Matthias

    2016-01-01

    Neuroblastoma is a malignant paediatric tumour of the sympathetic nervous system1. Roughly half of these tumours regress spontaneously or are cured by limited therapy. By contrast, high-risk neuroblastomas have an unfavourable clinical course despite intensive multimodal treatment, and their molecular basis has remained largely elusive2–4. Here we have performed whole-genome sequencing of 56 neuroblastomas (high-risk, n = 39; low-risk, n = 17) and discovered recurrent genomic rearrangements affecting a chromosomal region at 5p15.33 proximal of the telomerase reverse transcriptase gene (TERT). These rearrangements occurred only in high-risk neuroblastomas (12/39, 31%) in a mutually exclusive fashion with MYCN amplifications and ATRX mutations, which are known genetic events in this tumour type1,2,5. In an extended case series (n = 217), TERT rearrangements defined a subgroup of high-risk tumours with particularly poor outcome. Despite a large structural diversity of these rearrangements, they all induced massive transcriptional upregulation of TERT. In the remaining high-risk tumours, TERT expression was also elevated in MYCN-amplified tumours, whereas alternative lengthening of telomeres was present in neuroblastomas without TERT or MYCN alterations, suggesting that telomere lengthening represents a central mechanism defining this subtype. The 5p15.33 rearrangements juxtapose the TERT coding sequence to strong enhancer elements, resulting in massive chromatin remodelling and DNA methylation of the affected region. Supporting a functional role of TERT, neuroblastoma cell lines bearing rearrangements or amplified MYCN exhibited both upregulated TERT expression and enzymatic telomerase activity. In summary, our findings show that remodelling of the genomic context abrogates transcriptional silencing of TERT in high-risk neuroblastoma and places telomerase activation in the centre of transformation in a large fraction of these tumours. PMID:26466568

  4. Identification of ALK as the Major Familial Neuroblastoma Predisposition Gene

    Science.gov (United States)

    Mossë, Yalë P; Laudenslager, Marci; Longo, Luca; Cole, Kristina A; Wood, Andrew; Attiyeh, Edward F; Laquaglia, Michael J; Sennett, Rachel; Lynch, Jill E; Perri, Patrizia; Laureys, Geneviève; Speleman, Frank; Hakonarson, Hakon; Torkamani, Ali; Schork, Nicholas J; Brodeur, Garrett M; Tonini, Gian Paolo; Rappaport, Eric; Devoto, Marcella; Maris, John M

    2009-01-01

    SUMMARY Survival rates for the childhood cancer neuroblastoma have not substantively improved despite dramatic escalation in chemotherapy intensity. Like most human cancers, this embryonal malignancy can be inherited, but the genetic etiology of familial and sporadically occurring neuroblastoma was largely unknown. Here we show that germline mutations in the anaplastic lymphoma kinase gene (ALK) explain the majority of hereditary neuroblastomas, and that activating mutations can also be somatically acquired. We first identified a significant linkage signal at the short arm of chromosome 2 (maximum nonparametric LOD=4.23 at rs1344063) using a whole-genome scan in neuroblastoma pedigrees. Resequencing of regional candidate genes identified three separate missense mutations in the tyrosine kinase domain of ALK (G1128A, R1192P and R1275Q) that segregated with the disease in eight separate families. Examination of 491 sporadically occurring human neuroblastoma samples showed that the ALK locus was gained in 22.8%, and highly amplified in an additional 3.3%, and that these aberrations were highly associated with death from disease (P=0.0003). Resequencing of 194 high-risk neuroblastoma samples showed somatically acquired mutations within the tyrosine kinase domain in 12.4%. Nine of the ten mutations map to critical regions of the kinase domain and were predicted to be oncogenic drivers with high probability. Mutations resulted in constitutive phosphorylation consistent with activation, and targeted knockdown of ALK mRNA resulted in profound growth inhibition of 4 of 4 cell lines harboring mutant or amplified ALK, as well as 2 of 6 wild type for ALK. Our results demonstrate that heritable mutations of ALK are the major cause of familial neuroblastoma, and that germline or acquired activation of this cell surface kinase is a tractable therapeutic target for this lethal pediatric malignancy. PMID:18724359

  5. TrkAIII Promotes Microtubule Nucleation and Assembly at the Centrosome in SH-SY5Y Neuroblastoma Cells, Contributing to an Undifferentiated Anaplastic Phenotype

    Directory of Open Access Journals (Sweden)

    Antonietta R. Farina

    2013-01-01

    Full Text Available The alternative TrkAIII splice variant is expressed by advanced stage human neuroblastomas (NBs and exhibits oncogenic activity in NB models. In the present study, employing stable transfected cell lines and assays of indirect immunofluorescence, immunoprecipitation, Western blotting, microtubule regrowth, tubulin kinase, and tubulin polymerisation, we report that TrkAIII binds α-tubulin and promotes MT nucleation and assembly at the centrosome. This effect depends upon spontaneous TrkAIII activity, TrkAIII localisation to the centrosome and pericentrosomal area, and the capacity of TrkAIII to bind, phosphorylate, and polymerise tubulin. We propose that this novel role for TrkAIII contributes to MT involvement in the promotion and maintenance of an undifferentiated anaplastic NB cell morphology by restricting and augmenting MT nucleation and assembly at the centrosomal MTOC.

  6. Profile and outcome of neuroblastoma with convertional chemotherapy in children older than one year: a 15-years experience.

    Science.gov (United States)

    Bansal, Deepak; Marwaha, R K; Trehan, Amita; Rao, K L N; Gupta, Vishal

    2008-02-01

    The clinical profile and outcome of neuroblastoma in 103 children, older than one-year is presented. 74 had Stage IV, 27 Stage III and one patient each had Stage I or II disease. Treatment included chemotherapy followed by surgical resection/debulking. Radiotherapy was administered to those with residual tumor. Chemotherapy consisted of OPEC (vincristine, cyclophosphamide, cisplatin and etoposide). The caretakers of 54 (52.4%) children either did not opt for or defaulted therapy, whilst 3 patients died before chemotherapy could be initiated. Of the remaining 46 patients, the tumor progressed during therapy in 19 (41.3%). Relapse of disease was documented in 22 (47.8%) cases. Merely 4 (8.7%) children are disease free for a period of 16.5+/-6.7 months. Majority of children presented with advanced disease and the outcome was dismal with conventional non-myloablative chemotherapy.

  7. A comprehensive characterization of rare mitochondrial DNA variants in neuroblastoma.

    Science.gov (United States)

    Calabrese, Francesco Maria; Clima, Rosanna; Pignataro, Piero; Lasorsa, Vito Alessandro; Hogarty, Michael D; Castellano, Aurora; Conte, Massimo; Tonini, Gian Paolo; Iolascon, Achille; Gasparre, Giuseppe; Capasso, Mario

    2016-08-02

    Neuroblastoma, a tumor of the developing sympathetic nervous system, is a common childhood neoplasm that is often lethal. Mitochondrial DNA (mtDNA) mutations have been found in most tumors including neuroblastoma. We extracted mtDNA data from a cohort of neuroblastoma samples that had undergone Whole Exome Sequencing (WES) and also used snap-frozen samples in which mtDNA was entirely sequenced by Sanger technology. We next undertook the challenge of determining those mutations that are relevant to, or arisen during tumor development. The bioinformatics pipeline used to extract mitochondrial variants from matched tumor/blood samples was enriched by a set of filters inclusive of heteroplasmic fraction, nucleotide variability, and in silico prediction of pathogenicity. Our in silico multistep workflow applied both on WES and Sanger-sequenced neuroblastoma samples, allowed us to identify a limited burden of somatic and germline mitochondrial mutations with a potential pathogenic impact. The few singleton germline and somatic mitochondrial mutations emerged, according to our in silico analysis, do not appear to impact on the development of neuroblastoma. Our findings are consistent with the hypothesis that most mitochondrial somatic mutations can be considered as 'passengers' and consequently have no discernible effect in this type of cancer.

  8. Autoantibody signature differentiates Wilms tumor patients from neuroblastoma patients.

    Directory of Open Access Journals (Sweden)

    Jana Schmitt

    Full Text Available Several studies report autoantibody signatures in cancer. The majority of these studies analyzed adult tumors and compared the seroreactivity pattern of tumor patients with the pattern in healthy controls. Here, we compared the autoimmune response in patients with neuroblastoma and patients with Wilms tumor representing two different childhood tumors. We were able to differentiate untreated neuroblastoma patients from untreated Wilms tumor patients with an accuracy of 86.8%, a sensitivity of 87.0% and a specificity of 86.7%. The separation of treated neuroblastoma patients from treated Wilms tumor patients' yielded comparable results with an accuracy of 83.8%. We furthermore identified the antigens that contribute most to the differentiation between both tumor types. The analysis of these antigens revealed that neuroblastoma was considerably more immunogenic than Wilms tumor. The reported antigens have not been found to be relevant for comparative analyses between other tumors and controls. In summary, neuroblastoma appears as a highly immunogenic tumor as demonstrated by the extended number of antigens that separate this tumor from Wilms tumor.

  9. Neuroblastoma, a Paradigm for Big Data Science in Pediatric Oncology.

    Science.gov (United States)

    Salazar, Brittany M; Balczewski, Emily A; Ung, Choong Yong; Zhu, Shizhen

    2016-12-27

    Pediatric cancers rarely exhibit recurrent mutational events when compared to most adult cancers. This poses a challenge in understanding how cancers initiate, progress, and metastasize in early childhood. Also, due to limited detected driver mutations, it is difficult to benchmark key genes for drug development. In this review, we use neuroblastoma, a pediatric solid tumor of neural crest origin, as a paradigm for exploring "big data" applications in pediatric oncology. Computational strategies derived from big data science-network- and machine learning-based modeling and drug repositioning-hold the promise of shedding new light on the molecular mechanisms driving neuroblastoma pathogenesis and identifying potential therapeutics to combat this devastating disease. These strategies integrate robust data input, from genomic and transcriptomic studies, clinical data, and in vivo and in vitro experimental models specific to neuroblastoma and other types of cancers that closely mimic its biological characteristics. We discuss contexts in which "big data" and computational approaches, especially network-based modeling, may advance neuroblastoma research, describe currently available data and resources, and propose future models of strategic data collection and analyses for neuroblastoma and other related diseases.

  10. Neuroblastoma, a Paradigm for Big Data Science in Pediatric Oncology

    Directory of Open Access Journals (Sweden)

    Brittany M. Salazar

    2016-12-01

    Full Text Available Pediatric cancers rarely exhibit recurrent mutational events when compared to most adult cancers. This poses a challenge in understanding how cancers initiate, progress, and metastasize in early childhood. Also, due to limited detected driver mutations, it is difficult to benchmark key genes for drug development. In this review, we use neuroblastoma, a pediatric solid tumor of neural crest origin, as a paradigm for exploring “big data” applications in pediatric oncology. Computational strategies derived from big data science–network- and machine learning-based modeling and drug repositioning—hold the promise of shedding new light on the molecular mechanisms driving neuroblastoma pathogenesis and identifying potential therapeutics to combat this devastating disease. These strategies integrate robust data input, from genomic and transcriptomic studies, clinical data, and in vivo and in vitro experimental models specific to neuroblastoma and other types of cancers that closely mimic its biological characteristics. We discuss contexts in which “big data” and computational approaches, especially network-based modeling, may advance neuroblastoma research, describe currently available data and resources, and propose future models of strategic data collection and analyses for neuroblastoma and other related diseases.

  11. TIAM1 variants improve clinical outcome in neuroblastoma.

    Science.gov (United States)

    Sanmartín, Elena; Yáñez, Yania; Fornés-Ferrer, Victoria; Zugaza, José L; Cañete, Adela; Castel, Victoria; Font de Mora, Jaime

    2017-07-11

    Identification of tumor driver mutations is crucial for improving clinical outcome using a personalized approach to the treatment of cancer. Neuroblastoma is a tumor of the peripheral sympathetic nervous system for which only a few driver alterations have been described including MYCN amplification and ALK mutations. We assessed 106 primary neuroblastoma tumors by next generation sequencing using a customized amplicon-based gene panel. Our results reveal that genetic variants in TIAM1 gene associate with better clinical outcome, suggesting a role for these TIAM1 variants in preventing progression of this disease. The detected variants are located within the different domains of TIAM1 that signal to the upstream regulator RAS and downstream effector molecules MYC and RAC, which are all implicated in neuroblastoma etiology and progression. Clinical outcome was improved in tumors where a TIAM1 variant was present concomitantly with either ALK mutation or MYCN amplification. Given the function of these signaling molecules in cell survival, proliferation, differentiation and neurite outgrowth, our data suggest that the TIAM1-mediated network is essential to neuroblastoma and thus, inhibiting TIAM1 reflects a rational strategy for improving therapy efficacy in neuroblastoma.

  12. Stage 4S neuroblastoma, a disseminated tumor with excellent outcome

    International Nuclear Information System (INIS)

    Elimam, Najla A.; Atra, Ayad A.; Fayea, Najwa Y.; Al-Asaad, Tareq G.; Khattab, Taha M.; Al-Sulami, Ganadeel A.; Felimban, Sami K.

    2006-01-01

    To review the clinical features and outcome of all cases of stage 4S neuroblastoma treated at our center. We retrospectively reviewed the files of all patients (n=75) with neuroblastoma treated at King Abdul-Aziz Medical City, Jeddah, Kingdom of Saudi Arabia between 1986 and 2005. We studied the clinical features and outcome of patients with stage 4S neuroblastoma. Six patients (8%) were confirmed to have stage 4S neuroblastoma. Three were boys with a median age at diagnosis of 4.5 months (range 28 days-11 moths). Four patients required no intervention. The remaining 2 patients were treated chemotherapy due to progressive hepatomegaly and respiratory distress. No patient required radiotherapy or surgical intervention. With a median follow up of four years (range 9 months --- 15.5 years), all patients are alive and well. Two patients continue to have a residual abdominal mass, while complete resolution occurred in the others. Stage 4S neuroblastoma is special tumor that carries excellent prognosis. Spontaneous regression may occur and intervention is only required in symptomatic patients. (author)

  13. Advances in Risk Classification and Treatment Strategies for Neuroblastoma

    Science.gov (United States)

    Pinto, Navin R.; Applebaum, Mark A.; Volchenboum, Samuel L.; Matthay, Katherine K.; London, Wendy B.; Ambros, Peter F.; Nakagawara, Akira; Berthold, Frank; Schleiermacher, Gudrun; Park, Julie R.; Valteau-Couanet, Dominique; Pearson, Andrew D.J.

    2015-01-01

    Risk-based treatment approaches for neuroblastoma have been ongoing for decades. However, the criteria used to define risk in various institutional and cooperative groups were disparate, limiting the ability to compare clinical trial results. To mitigate this problem and enhance collaborative research, homogenous pretreatment patient cohorts have been defined by the International Neuroblastoma Risk Group classification system. During the past 30 years, increasingly intensive, multimodality approaches have been developed to treat patients who are classified as high risk, whereas patients with low- or intermediate-risk neuroblastoma have received reduced therapy. This treatment approach has resulted in improved outcome, although survival for high-risk patients remains poor, emphasizing the need for more effective treatments. Increased knowledge regarding the biology and genetic basis of neuroblastoma has led to the discovery of druggable targets and promising, new therapeutic approaches. Collaborative efforts of institutions and international cooperative groups have led to advances in our understanding of neuroblastoma biology, refinements in risk classification, and stratified treatment strategies, resulting in improved outcome. International collaboration will be even more critical when evaluating therapies designed to treat small cohorts of patients with rare actionable mutations. PMID:26304901

  14. Capsule-odometer: a concept to improve accurate lesion localisation.

    Science.gov (United States)

    Karargyris, Alexandros; Koulaouzidis, Anastasios

    2013-09-21

    In order to improve lesion localisation in small-bowel capsule endoscopy, a modified capsule design has been proposed incorporating localisation and - in theory - stabilization capabilities. The proposed design consists of a capsule fitted with protruding wheels attached to a spring-mechanism. This would act as a miniature odometer, leading to more accurate lesion localization information in relation to the onset of the investigation (spring expansion e.g., pyloric opening). Furthermore, this capsule could allow stabilization of the recorded video as any erratic, non-forward movement through the gut is minimised. Three-dimensional (3-D) printing technology was used to build a capsule prototype. Thereafter, miniature wheels were also 3-D printed and mounted on a spring which was attached to conventional capsule endoscopes for the purpose of this proof-of-concept experiment. In vitro and ex vivo experiments with porcine small-bowel are presented herein. Further experiments have been scheduled.

  15. Primary hepatocellular carcinoma localised by a radiolabelled monoclonal antibody

    Energy Technology Data Exchange (ETDEWEB)

    Markham, N; Ritson, A; James, O; Curtin, N; Bassendine, M; Sikora, K

    1986-01-01

    A rat monoclonal antibody, YPC2/38.8, was selected from a panel of antibodies derived by immunising rats with fresh human colorectal carcinoma. It was found to bind to a 30,000 dalton protein present on the cell surface of normal colon and liver. This protein was increased 10-fold on primary hepatocellular carcinoma (PHC) cells. After labelling with /sup 131/I, YPC2/38.8 was shown to localise human PHCs grown as xenografts in immunosuppressed mice. The authors conclude that YPC2/38.8 may have potential for diagnostic localisation and possibly thence for the selective targeting of drugs or toxins in patients with PHC arising in a liver unaffected by significant parenchymal disease. 16 refs.; 4 figs.; 1 table.

  16. Identification of membrane-type 1 matrix metalloproteinase tyrosine phosphorylation in association with neuroblastoma progression

    International Nuclear Information System (INIS)

    Nyalendo, Carine; Sartelet, Hervé; Barrette, Stéphane; Ohta, Shigeru; Gingras, Denis; Béliveau, Richard

    2009-01-01

    Neuroblastoma is a pediatric tumor of neural crest cells that is clinically characterized by its variable evolution, from spontaneous regression to malignancy. Despite many advances in neuroblastoma research, 60% of neuroblastoma, which are essentially metastatic cases, are associated with poor clinical outcome due to the lack of effectiveness of current therapeutic strategies. Membrane-type 1 matrix metalloproteinase (MT1-MMP, MMP-14), an enzyme involved in several steps in tumor progression, has previously been shown to be associated with poor clinical outcome for neuroblastoma. Based on our recent demonstration that MT1-MMP phosphorylation is involved in the growth of fibrosarcoma tumors, we examined the potential role of phosphorylated MT1-MMP in neuroblastoma progression. Tyrosine phosphorylated MT1-MMP was immunostained on tissue microarray samples from 55 patients with neuroblastoma detected by mass screening (known to be predominantly associated with favourable outcome), and from 234 patients with standard diagnosed neuroblastoma. In addition, the effects of a non phosphorylable version of MT1-MMP on neuroblastoma cell migration and proliferation were investigated within three-dimensional collagen matrices. Although there is no correlation between the extent of tyrosine phosphorylation of MT1-MMP (pMT1-MMP) and MYCN amplification or clinical stage, we observed greater phosphorylation of pMT1-MMP in standard neuroblastoma, while it is less evident in neuroblastoma from mass screening samples (P = 0.0006) or in neuroblastoma samples from patients younger than one year (P = 0.0002). In vitro experiments showed that overexpression of a non-phosphorylable version of MT1-MMP reduced MT1-MMP-mediated neuroblastoma cell migration and proliferation within a three-dimensional type I collagen matrix, suggesting a role for the phosphorylated enzyme in the invasive properties of neuroblastoma cells. Overall, these results suggest that tyrosine phosphorylated MT1-MMP

  17. [Robot-assisted liver resection].

    Science.gov (United States)

    Aselmann, H; Möller, T; Kersebaum, J-N; Egberts, J H; Croner, R; Brunner, M; Grützmann, R; Becker, T

    2017-06-01

    Robotic liver resection can overcome some of the limitations of laparoscopic liver surgery; therefore, it is a promising tool to increase the proportion of minimally invasive liver resections. The present article gives an overview of the current literature. Furthermore, the results of a nationwide survey on robotic liver surgery among hospitals in Germany with a DaVinci system used in general visceral surgery and the perioperative results of two German robotic centers are presented.

  18. La Carte de Localisation Probable des Avalanches (CPLA

    Directory of Open Access Journals (Sweden)

    Gilles BORREL

    1994-12-01

    Full Text Available La Carte de Localisation Probable des Avalanches (CPLA indique l’enveloppe des limites extrêmes connues atteintes par les avalanches, ainsi que les travaux de protection associés. Il s’agit d’un document informatif et non d’une carte de risque. Depuis 1990, les données thématiques sont numérisées.

  19. Endoscopic Transsphenoidal Resection of Craniopharyngioma.

    Science.gov (United States)

    Liew, Kong Yew; Narayanan, Prepageran; Waran, Vicknes

    2018-02-01

    Objectives  To demonstrate, step-by-step, the technique and efficacy of endoscopic transsphenoidal approach in resection of a suprasellar craniopharyngioma. Design  The video shows a step-by-step approach to the resection, covering the exposure, access, resection, and confirmation of resection and reconstruction. Setting  The surgery was performed in the University of Malaya Medical Centre, a tertiary referral center in the capital of Malaysia. Participants  Surgery was performed jointly by Professor Prepageran from the department of otorhinolaryngology and Professor Vicknes Waran from the division of neurosurgery. Both surgeons are from the University of Malaya. Video compilation, editing, and voice narration was done by Dr. Kong Yew Liew. Main Outcome Measures  Completeness of resection and avoidance of intra- and postoperative complications. Results  Based on intraoperative views and MRI findings, the tumor was completely resected with the patient suffering only transient diabetes insipidus. Conclusion  Central suprasellar tumors can be removed completely via an endoscopic transsphenoidal approach with minimal morbidity to the patient. The link to the video can be found at: https://youtu.be/ZNIHfk12cYg .

  20. Kyste hydatique à localisation costo vertébrale

    Science.gov (United States)

    Marouf, Rachid

    2014-01-01

    L'hydatidose est une affection parasitaire due à la contamination de l'homme par la forme larvaire de ténia échinococcus granulosus, la forme costo vertébrale est une localisation très rare qui représente 0,18 à 1,21% de l'ensemble des localisations hydatiques. Nous rapportons le cas d'une femme de 32 ans qui présente un kyste hydatique multi vésiculaire à localisation costovertébrale, traité par chirurgie radicale associée à un traitement médical anti parasitaire pour une durée de 6 mois, avec bonne évolution. L'atteinte costo-vertébrale par la maladie hydatique est rare et l’évolution est insidieuse. Malgré un traitement chirurgical radical, la fréquence des récidives rend le pronostic sombre. PMID:25922632

  1. Somatic PTPN11 Mutation in a Child With Neuroblastoma and Protein Losing Enteropathy.

    Science.gov (United States)

    Obasaju, Patience; Brondon, Jennifer; Mir, Sabina; Fordham, Lynn A; Lee, Sang; Blatt, Julie

    2018-05-01

    Neuroblastoma and protein losing enteropathy (PLE) are diagnoses commonly seen by oncologists and gastroenterologists, respectively. The concurrence of these 2 entities is rare, and not well explained. We describe the sixth case of PLE in a child with neuroblastoma, and the first for which genetic information is available. Tumor DNA had a mutation in the PTPN11 gene, which has been described in neuroblastoma, and in Noonan syndrome-a diagnosis in which neuroblastoma and PLE independently have been reported. Constitutional DNA was normal. Genetic studies in future patients will be needed to support the link between neuroblastoma and PLE.

  2. Pancreatic Metastasis in a Child Suffering with Treated Stage 4 Neuroblastoma

    International Nuclear Information System (INIS)

    Kim, Eun Young; Yoo, So Young; Kim, Ji Hye; Sung, Ki Woong

    2008-01-01

    Neuroblastoma is the most common extracranial solid tumor of childhood, and its metastasis to distant organs such as bone, bone marrow and liver is well documented. However, pancreatic metastasis of neuroblastoma has not yet been reported in the medical literature. We report here on a 4-year old boy who had a metastatic relapse in his pancreas, combined with pancreatitis, after remission of stage 4 neuroblastoma. In conclusion, we present here a very rare case of neuroblastoma that metastasized to the pancreas in a 4- year-old boy. Pancreatic metastasis should be taken into consideration for those patients who are found to have pancreatic nodules concurrent with neuroblastoma

  3. Significance of clinical and biologic features in Stage 3 neuroblastoma: a report from the International Neuroblastoma Risk Group project.

    Science.gov (United States)

    Meany, Holly J; London, Wendy B; Ambros, Peter F; Matthay, Katherine K; Monclair, Tom; Simon, Thorsten; Garaventa, Alberto; Berthold, Frank; Nakagawara, Akira; Cohn, Susan L; Pearson, Andrew D J; Park, Julie R

    2014-11-01

    International Neuroblastoma Staging System (INSS) Stage 3 neuroblastoma is a heterogeneous disease. Data from the International Neuroblastoma Risk Group (INRG) database were analyzed to define patient and tumor characteristics predictive of outcome. Of 8,800 patients in the INRG database, 1,483 with INSS Stage 3 neuroblastoma and complete follow-up data were analyzed. Secondary analysis was performed in 1,013 patients (68%) with MYCN-non-amplified (NA) tumors. Significant prognostic factors were identified via log-rank test comparisons of survival curves. Multivariable Cox proportional hazards regression model was used to identify factors independently predictive of event-free survival (EFS). Age at diagnosis (P INSS Stage 3 neuroblastoma patients, age at diagnosis, MYCN status and histology predict outcome. Patients <547 days of age with MYCN-NA tumors that lack chromosome 11q aberrations or those with serum ferritin <96 ng/ml have excellent prognosis and should be considered for therapy reduction. Prospective clinical trials are needed to identify optimal therapy for those patients ≥ 547 days of age with undifferentiated histology or elevated serum ferritin. © 2014 Wiley Periodicals, Inc.

  4. Neuroblastoma trial to overcome a rare malignant disease

    International Nuclear Information System (INIS)

    Fukushima, Takashi; Shichino, Hiroyuki; Kumagai, Masaaki

    2007-01-01

    Neuroblastoma is one of the main causes of children's deaths in Japan and many developed countries, although it is a rather rare pediatric cancer. Many clinical studies have been carried out and reported. The clinical study system of Japan is much different from the systems of the other countries. In Japan, the main hospitals, where clinical study including clinical trials have been conducted, are not only national centers but also many regional or prefectural centers. Progression-free survival has been achieved in over 80% of low-risk patients, and in about 40% of high-risk patients. These are the same as the outcomes of neuroblastoma patients in European countries and North America. Further clinical studies and translational research should be planned especially regarding high-risk neuroblastomas. (author)

  5. A Hybrid Robotic Control System Using Neuroblastoma Cultures

    Science.gov (United States)

    Ferrández, J. M.; Lorente, V.; Cuadra, J. M.; Delapaz, F.; Álvarez-Sánchez, José Ramón; Fernández, E.

    The main objective of this work is to analyze the computing capabilities of human neuroblastoma cultured cells and to define connection schemes for controlling a robot behavior. Multielectrode Array (MEA) setups have been designed for direct culturing neural cells over silicon or glass substrates, providing the capability to stimulate and record simultaneously populations of neural cells. This paper describes the process of growing human neuroblastoma cells over MEA substrates and tries to modulate the natural physiologic responses of these cells by tetanic stimulation of the culture. We show that the large neuroblastoma networks developed in cultured MEAs are capable of learning: establishing numerous and dynamic connections, with modifiability induced by external stimuli and we propose an hybrid system for controlling a robot to avoid obstacles.

  6. I-131 metaiodobenzylguanidine: diagnostic use in neuroblastoma patients in relapse

    International Nuclear Information System (INIS)

    Heyman, S.; Evans, A.E.; D'Angio, G.J.

    1988-01-01

    Metaiodobenzylguanidine (MIBG) has been used for the detection and treatment of neuroectodermal tumors, including neuroblastoma. We report our experience with 131 I-MIBG used diagnostically in neuroblastoma patients with relapse. Thirty-eight studies were performed in 26 patients. There were 24 children (range 3 months-14 years) and two adults. While the study was found to be both sensitive and specific for the presence of disease, there are instances of discordance. False-negative studies were found with a markedly anaplastic tumor and with two mature ganglioneuromas. A bone lesion was negative with 131 I-MIBG, but positive on bone scan. A biopsy confirmed the presence of neuroblastoma. Caution should be exercised when scanning pretreated patients, and perhaps with newly diagnosed patients as well

  7. Anti-angiogenic SPARC peptides inhibit progression of neuroblastoma tumors

    Directory of Open Access Journals (Sweden)

    Tian Yufeng

    2010-06-01

    Full Text Available Abstract Background New, more effective strategies are needed to treat highly aggressive neuroblastoma. Our laboratory has previously shown that full-length Secreted Protein Acidic and Rich in Cysteine (SPARC and a SPARC peptide corresponding to the follistatin domain of the protein (FS-E potently block angiogenesis and inhibit the growth of neuroblastoma tumors in preclinical models. Peptide FS-E is structurally complex and difficult to produce, limiting its potential as a therapeutic in the clinic. Results In this study, we synthesized two smaller and structurally more simple SPARC peptides, FSEN and FSEC, that respectively correspond to the N-and C-terminal loops of peptide FS-E. We show that both peptides FSEN and FSEC have anti-angiogenic activity in vitro and in vivo, although FSEC is more potent. Peptide FSEC also significantly inhibited the growth of neuroblastoma xenografts. Histologic examination demonstrated characteristic features of tumor angiogenesis with structurally abnormal, tortuous blood vessels in control neuroblastoma xenografts. In contrast, the blood vessels observed in tumors, treated with SPARC peptides, were thin walled and structurally more normal. Using a novel method to quantitatively assess blood vessel abnormality we demonstrated that both SPARC peptides induced changes in blood vessel architecture that are consistent with blood vessel normalization. Conclusion Our results demonstrate that SPARC peptide FSEC has potent anti-angiogenic and anti-tumorigenic effects in neuroblastoma. Its simple structure and ease of production indicate that it may have clinical utility in the treatment of high-risk neuroblastoma and other types of pediatric and adult cancers, which depend on angiogenesis.

  8. Dinutuximab in the Treatment of High-Risk Neuroblastoma in Children

    Directory of Open Access Journals (Sweden)

    Hazal Gur

    2017-06-01

    Full Text Available Neuroblastoma is the most common extracranial tumor derived from neural crest cells in childhood, and treatment of high-risk neuroblastoma is a difficulty in oncology field. The discovery of new treatment strategies to treat pediatric patients with high-risk neuroblastoma is important. Dinutuximab (ch14.18; Unituxin, a chimeric human-mouse monoclonal antibody, is approved by Food and Drug Administration in 2015 to be used specifically in the treatment of high-risk neuroblastoma. It binds the disialoganglioside (GD2 antigen on the surface of neuroblastoma cells and induces lysis of GD2-expressed neuroblastoma cells via antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity. To enhance its activity, it is used with a combination of granulocyte-macrophage colony-stimulating factor, interleukin 2, and 13- cis -retinoic acid. In this review, we discuss the use of dinutuximab in the treatment of high-risk neuroblastoma.

  9. Lung Metastases in Neuroblastoma at Initial Diagnosis: A Report from the International Neuroblastoma Risk Group (INRG) Project

    Science.gov (United States)

    DuBois, Steven G.; London, Wendy B.; Zhang, Yang; Matthay, Katherine K.; Monclair, Tom; Ambros, Peter F.; Cohn, Susan L.; Pearson, Andrew; Diller, Lisa

    2009-01-01

    Background Neuroblastoma is the most common extracranial pediatric solid cancer. Lung metastasis is rarely detected in children with newly diagnosed neuroblastoma. We aimed to describe the incidence, clinical characteristics, and outcome of patients with lung metastasis at initial diagnosis using a large international database. Procedure The subset of patients from the International Neuroblastoma Risk Group database with INSS stage 4 neuroblastoma and known data regarding lung metastasis at diagnosis was selected for analysis. Clinical and biological characteristics were compared between patients with and without lung metastasis. Survival for patients with and without lung metastasis was estimated by Kaplan-Meier methods. Cox proportional hazards methods were used to determine the independent prognostic value of lung metastasis at diagnosis. Results Of the 2,808 patients with INSS stage 4 neuroblastoma diagnosed between 1990 and 2002, 100 patients (3.6%) were reported to have lung metastasis at diagnosis. Lung metastasis was more common among patients with MYCN amplified tumors, adrenal primary tumors, or elevated lactate dehydrogenase (LDH) levels (p < 0.02 in each case). Five-year overall survival ± standard error for patients with lung metastasis was 34.5% ± 6.8% compared to 44.7% ± 1.3% for patients without lung metastasis (p=0.0002). However, in multivariable analysis, the presence of lung metastasis was not independently predictive of outcome. Conclusions Lung metastasis at initial diagnosis of neuroblastoma is associated with MYCN amplification and elevated LDH levels. Although lung metastasis at diagnosis was not independently predictive of outcome in this analysis, it remains a useful prognostic marker of unfavorable outcome. PMID:18649370

  10. Presenilin expression during induced differentiation of the human neuroblastoma SH-SY5Y cell line.

    Science.gov (United States)

    Flood, Fiona; Sundström, Erik; Samuelsson, Eva-Britt; Wiehager, Birgitta; Seiger, Ake; Johnston, Janet A; Cowburn, Richard F

    2004-06-01

    Human neuroblastoma SH-SY5Y cells stably transfected with both wild-type and exon-9 deleted (deltaE9) presenilin constructs were used to study the role of the presenilin proteins during differentiation. Cells transfected with either wild-type or deltaE9 PS1, of which the latter abolishes normal endoproteolytic cleavage of the protein, showed no obvious differences in their ability to differentiate to a neuronal-like phenotype upon treatment with retinoic acid (RA). A defined pattern of PS1 expression was observed during differentiation with both RA and the phorbol ester TPA. Full-length PS1 was shown to increase dramatically within 5-24 h of RA treatment. TPA gave an earlier and longer lasting increase in full-length PS1 levels. The intracellular distribution pattern of PS1 was markedly altered following RA treatment. Within 24h PS1 was highly up-regulated throughout the cell body around the nucleus. Between 2 and 4 weeks PS1 staining appeared punctate and also localised to the nucleus. Increases in PS1 expression upon treatment with RA and TPA were blocked by treatment with cycloheximide, indicating a role of de-novo protein synthesis in this effect. PS2 expression remained unchanged during differentiation. Levels of full-length PS1 were also seen to increase during neurogenesis and neuronal differentiation in the forebrain of first trimester human foetuses between 6.5 and 11 weeks. These combined observations support the idea that PS1 is involved in neuronal differentiation by a mechanism likely independent of endoproteolysis of the protein.

  11. Clinical characteristics and outcome of patients with neuroblastoma presenting genomic amplification of loci other than MYCN.

    Directory of Open Access Journals (Sweden)

    Anne Guimier

    Full Text Available Somatically acquired genomic alterations with MYCN amplification (MNA are key features of neuroblastoma (NB, the most common extra-cranial malignant tumour of childhood. Little is known about the frequency, clinical characteristics and outcome of NBs harbouring genomic amplification(s distinct from MYCN.Genomic profiles of 1100 NBs from French centres studied by array-CGH were re-examined specifically to identify regional amplifications. Patients were included if amplifications distinct from the MYCN locus were seen. A subset of NBs treated at Institut Curie and harbouring MNA as determined by array-CGH without other amplification was also studied. Clinical and histology data were retrospectively collected.In total, 56 patients were included and categorised into 3 groups. Group 1 (n = 8 presented regional amplification(s without MNA. Locus 12q13-14 was a recurrent amplified region (4/8 cases. This group was heterogeneous in terms of INSS stages, primary localisations and histology, with atypical clinical features. Group 2 (n = 26 had MNA as well as other regional amplifications. These patients shared clinical features of those of a group of NBs MYCN amplified (Group 3, n = 22. Overall survival for group 1 was better than that of groups 2 and 3 (5 year OS: 87.5%±11% vs 34.9%±7%, log-rank p<0.05.NBs harbouring regional amplification(s without MNA are rare and seem to show atypical features in clinical presentation and genomic profile. Further high resolution genetic explorations are justified in this heterogeneous group, especially when considering these alterations as predictive markers for targeted therapy.

  12. Clinical Characteristics and Outcome of Patients with Neuroblastoma Presenting Genomic Amplification of Loci Other than MYCN

    Science.gov (United States)

    Guimier, Anne; Ferrand, Sandrine; Pierron, Gaëlle; Couturier, Jérôme; Janoueix-Lerosey, Isabelle; Combaret, Valérie; Mosseri, Véronique; Thebaud, Estelle; Gambart, Marion; Plantaz, Dominique; Marabelle, Aurélien; Coze, Carole; Rialland, Xavier; Fasola, Sylvie; Lapouble, Eve; Fréneaux, Paul; Peuchmaur, Michel; Michon, Jean; Delattre, Olivier; Schleiermacher, Gudrun

    2014-01-01

    Background Somatically acquired genomic alterations with MYCN amplification (MNA) are key features of neuroblastoma (NB), the most common extra-cranial malignant tumour of childhood. Little is known about the frequency, clinical characteristics and outcome of NBs harbouring genomic amplification(s) distinct from MYCN. Methods Genomic profiles of 1100 NBs from French centres studied by array-CGH were re-examined specifically to identify regional amplifications. Patients were included if amplifications distinct from the MYCN locus were seen. A subset of NBs treated at Institut Curie and harbouring MNA as determined by array-CGH without other amplification was also studied. Clinical and histology data were retrospectively collected. Results In total, 56 patients were included and categorised into 3 groups. Group 1 (n = 8) presented regional amplification(s) without MNA. Locus 12q13-14 was a recurrent amplified region (4/8 cases). This group was heterogeneous in terms of INSS stages, primary localisations and histology, with atypical clinical features. Group 2 (n = 26) had MNA as well as other regional amplifications. These patients shared clinical features of those of a group of NBs MYCN amplified (Group 3, n = 22). Overall survival for group 1 was better than that of groups 2 and 3 (5 year OS: 87.5%±11% vs 34.9%±7%, log-rank p<0.05). Conclusion NBs harbouring regional amplification(s) without MNA are rare and seem to show atypical features in clinical presentation and genomic profile. Further high resolution genetic explorations are justified in this heterogeneous group, especially when considering these alterations as predictive markers for targeted therapy. PMID:25013904

  13. Hedgehog signaling pathway in neuroblastoma differentiation.

    Science.gov (United States)

    Souzaki, Ryota; Tajiri, Tatsuro; Souzaki, Masae; Kinoshita, Yoshiaki; Tanaka, Sakura; Kohashi, Kenichi; Oda, Yoshinao; Katano, Mitsuo; Taguchi, Tomoaki

    2010-12-01

    The hedgehog (Hh) signaling pathway is activated in some adult cancers. On the other hand, the Hh signaling pathway plays an important role in the development of the neural crest in embryos. The aim of this study is to show the activation of Hh signaling pathway in neuroblastoma (NB), a pediatric malignancy arising from neural crest cells, and to reveal the meaning of the Hh signaling pathway in NB development. This study analyzed the expression of Sonic hedgehog (Shh), GLI1, and Patched 1 (Ptch1), transactivators of Hh signaling pathway, by immunohistochemistry in 82 NB and 10 ganglioneuroblastoma cases. All 92 cases were evaluated for the status of MYCN amplification. Of the 92 cases, 67 (73%) were positive for Shh, 62 cases (67%) were positive for GLI1, and 73 cases (79%) were positive for Ptch1. Only 2 (10%) of the 20 cases with MYCN amplification were positive for Shh and GLI1, and 4 cases (20%) were positive for Ptch1 (MYCN amplification vs no MYCN amplification, P ≦ .01). The percentage of GLI1-positive cells in the cases with INSS stage 1 without MYCN amplification was significantly higher than that with INSS stage 4. Of 72 cases without MYCN amplification, 60 were GLI1-positive. Twelve cases were GLI1-negative, and the prognosis of the GLI1-positive cases was significantly better than that of the GLI1-negative cases (P = .015). Most of NBs without MYCN amplification were positive for Shh, GLI1, and Ptch1. In the cases without MYCN amplification, the high expression of GLI1 was significantly associated with early clinical stage and a good prognosis of the patients. In contrast to adult cancers, the activation of the Hh signaling pathway in NB may be associated with the differentiation of the NB. Copyright © 2010 Elsevier Inc. All rights reserved.

  14. A comparison of targeting of neuroblastoma with mIBG and anti L1-CAM antibody mAb chCE7: therapeutic efficacy in a neuroblastoma xenograft model and imaging of neuroblastoma patients

    NARCIS (Netherlands)

    Hoefnagel, C. A.; Rutgers, M.; Buitenhuis, C. K.; Smets, L. A.; de Kraker, J.; Meli, M.; Carrel, F.; Amstutz, H.; Schubiger, P. A.; Novak-Hofer, I.

    2001-01-01

    Iodine-131 labelled anti L1-CAM antibody mAb chCE7 was compared with the effective neuroblastoma-seeking agent 131I-labelled metaiodobenzylguanidine (MIBG) with regard to (a) its therapeutic efficacy in treating nude mice with neuroblastoma xenografts and (b) its tumour targeting ability in

  15. Three-dimensional segmentation of the tumor mass in computed tomographic images of neuroblastoma

    Science.gov (United States)

    Deglint, Hanford J.; Rangayyan, Rangaraj M.; Boag, Graham S.

    2004-05-01

    Tumor definition and diagnosis require the analysis of the spatial distribution and Hounsfield unit (HU) values of voxels in computed tomography (CT) images, coupled with a knowledge of normal anatomy. Segmentation of the tumor in neuroblastoma is complicated by the fact that the mass is almost always heterogeneous in nature; furthermore, viable tumor, necrosis, fibrosis, and normal tissue are often intermixed. Rather than attempt to separate these tissue types into distinct regions, we propose to explore methods to delineate the normal structures expected in abdominal CT images, remove them from further consideration, and examine the remaining parts of the images for the tumor mass. We explore the use of fuzzy connectivity for this purpose. Expert knowledge provided by the radiologist in the form of the expected structures and their shapes, HU values, and radiological characteristics are also incorporated in the segmentation algorithm. Segmentation and analysis of the tissue composition of the tumor can assist in quantitative assessment of the response to chemotherapy and in the planning of delayed surgery for resection of the tumor. The performance of the algorithm is evaluated using cases acquired from the Alberta Children's Hospital.

  16. Channelrhodopsin-2 localised to the axon initial segment.

    Directory of Open Access Journals (Sweden)

    Matthew S Grubb

    2010-10-01

    Full Text Available The light-gated cation channel Channelrhodopsin-2 (ChR2 is a powerful and versatile tool for controlling neuronal activity. Currently available versions of ChR2 either distribute uniformly throughout the plasma membrane or are localised specifically to somatodendritic or synaptic domains. Localising ChR2 instead to the axon initial segment (AIS could prove an extremely useful addition to the optogenetic repertoire, targeting the channel directly to the site of action potential initiation, and limiting depolarisation and associated calcium entry elsewhere in the neuron. Here, we describe a ChR2 construct that we localised specifically to the AIS by adding the ankyrinG-binding loop of voltage-gated sodium channels (Na(vII-III to its intracellular terminus. Expression of ChR2-YFP-Na(vII-III did not significantly affect the passive or active electrical properties of cultured rat hippocampal neurons. However, the tiny ChR2 currents and small membrane depolarisations resulting from AIS targeting meant that optogenetic control of action potential firing with ChR2-YFP-Na(vII-III was unsuccessful in baseline conditions. We did succeed in stimulating action potentials with light in some ChR2-YFP-Na(vII-III-expressing neurons, but only when blocking KCNQ voltage-gated potassium channels. We discuss possible alternative approaches to obtaining precise control of neuronal spiking with AIS-targeted optogenetic constructs and propose potential uses for our ChR2-YFP-Na(vII-III probe where subthreshold modulation of action potential initiation is desirable.

  17. Orthogonal views improves localisation in bone scans of wrist

    International Nuclear Information System (INIS)

    Roth, A.L.

    1997-01-01

    Full text: Of all nuclear medicine studies, bone scans are the most fundamental. However, straightforward these may seem, there are always mechanisms that can be implemented which assist in a more precise diagnosis, particularly in areas with an intricate bone structure. An 18-year-old right-handed student presented to her doctor with a one month history of pain over the right distal radio-ulna joint area. Clinically, she had prominence of the right ulna, which suggested that there may have been a previous injury to the wrist. Also, pronation/supination were painful where there was swelling of the extensor carpi ulnaris tendon, as well as some discomfort with clicking in ulna deviation/rotation. The X-rays demonstrated some premature radial epiphysial closure. A bone scan was requested to attempt to localise the main inflammatory focus. The dynamic study was performed in the planar projection with an immediate blood pool for 300k being taken. These demonstrated a vascular blush medially. A medial blood pool image was acquired and it localised the abnormal vascularity as being dorsal. A separate focal area of less intense blood pooling was also noted in the line of the distal ulna. Delayed images showed increased uptake localised to the ulna styloid. Anatomically, the superficial vascular blush correlated with tenosynovitis. Hence, the orthogonal initial and delayed images were definitive in the diagnoses of tenosynovitis of the extensor carpi ulnaris tendon. This clearly complements the information provided by the palmar view. However, it is important to remember that an increased radiation dose to the technologist is incurred as a result of the extra orthogonal view, hence attention to technique is imperative

  18. Orthogonal views improves localisation in bone scans of wrist

    Energy Technology Data Exchange (ETDEWEB)

    Roth, A.L.

    1997-09-01

    Full text: Of all nuclear medicine studies, bone scans are the most fundamental. However, straightforward these may seem, there are always mechanisms that can be implemented which assist in a more precise diagnosis, particularly in areas with an intricate bone structure. An 18-year-old right-handed student presented to her doctor with a one month history of pain over the right distal radio-ulna joint area. Clinically, she had prominence of the right ulna, which suggested that there may have been a previous injury to the wrist. Also, pronation/supination were painful where there was swelling of the extensor carpi ulnaris tendon, as well as some discomfort with clicking in ulna deviation/rotation. The X-rays demonstrated some premature radial epiphysial closure. A bone scan was requested to attempt to localise the main inflammatory focus. The dynamic study was performed in the planar projection with an immediate blood pool for 300k being taken. These demonstrated a vascular blush medially. A medial blood pool image was acquired and it localised the abnormal vascularity as being dorsal. A separate focal area of less intense blood pooling was also noted in the line of the distal ulna. Delayed images showed increased uptake localised to the ulna styloid. Anatomically, the superficial vascular blush correlated with tenosynovitis. Hence, the orthogonal initial and delayed images were definitive in the diagnoses of tenosynovitis of the extensor carpi ulnaris tendon. This clearly complements the information provided by the palmar view. However, it is important to remember that an increased radiation dose to the technologist is incurred as a result of the extra orthogonal view, hence attention to technique is imperative.

  19. KIF1Bβ and Neuroblastoma: Failure to Divide and Cull

    OpenAIRE

    Blackstone, Craig

    2016-01-01

    Neuroblastomas are associated with KIF1Bβ mutations within tumor suppressor region 1p36. In this issue of Developmental Cell, Li et al. (2016) show that KIF1Bβ binding releases calcineurin autoinhibition, leading to dephosphorylation of the DRP1 GTPase and subsequent mitochondrial fragmentation. KIF1Bβ impairment causes mitochondrial hyperfusion, impairing developmental apoptosis and promoting tumorigenesis.

  20. Intracranial route of a cervical neuroblastoma through skull base foramina

    International Nuclear Information System (INIS)

    Goldberg, R.M.; Keller, I.A.; Schonfeld, S.M.; Mezrich, R.S.; Rosenfeld, D.L.

    1996-01-01

    A case of primary cervical neuroblastoma gaining access to the cerebellopontine angle via direct perineural spread is described. MRI effectively delineated soft tissues, while CT demonstrated tumor calcifications and the integrity of adjacent bones. Both imaging modalities were beneficial in predicting the unique histology and pattern of disease confirmed at surgery. (orig.). With 1 fig

  1. Discovery – Ch14.18 Immunotherapy to Treat Neuroblastoma

    Science.gov (United States)

    Neuroblastoma is rare yet it's the most common cancer affecting infants. Prior to a discovery 20 years in the making, there was little hope for survival in children with advanced stages of the disease. Today, research is leading to a brighter outlook.

  2. Parenteral Nutrition in Liver Resection

    Directory of Open Access Journals (Sweden)

    Carlo Chiarla

    2012-01-01

    Full Text Available Albeit a very large number of experiments have assessed the impact of various substrates on liver regeneration after partial hepatectomy, a limited number of clinical studies have evaluated artificial nutrition in liver resection patients. This is a peculiar topic because many patients do not need artificial nutrition, while several patients need it because of malnutrition and/or prolonged inability to feeding caused by complications. The optimal nutritional regimen to support liver regeneration, within other postoperative problems or complications, is not yet exactly defined. This short review addresses relevant aspects and potential developments in the issue of postoperative parenteral nutrition after liver resection.

  3. Localised corrosion in AA 2099-T83 aluminium-lithium alloy: The role of grain orientation

    International Nuclear Information System (INIS)

    Ma, Y.; Zhou, X.; Liao, Y.; Yi, Y.; Wu, H.; Wang, Z.; Huang, W.

    2016-01-01

    Highlights: • Schmid factor of the grain/subgrain can indicate its corrosion susceptibility. • The localised corrosion prefers the grain with relatively large Schmid factor. • The localised corrosion is related to selective dissolution of T_1 phase. - Abstract: The mechanism for localised corrosion in AA 2099-T83 alloy during immersion in 3.5% NaCl solution is investigated. It is found that localised corrosion tends to occur in the grain with relatively large Schmid factor. The localised corrosion is related to selective dissolution of T_1 (Al_2CuLi) phase that preferentially precipitates at grain/subgrain boundaries and dislocations within grain interiors. A model is proposed to explain the development of the localised corrosion in the alloy by taking into account heterogeneous plastic deformation during cold working and preferential precipitation of T_1 phase at crystallographic defects within deformed grains.

  4. Suppressing proton decay in theories with localised fermions

    International Nuclear Information System (INIS)

    Acharya, B.S.; Valandro, R.

    2005-12-01

    We calculate the contribution to the proton decay amplitude from Kaluza-Klein lepto-quarks in theories with extra dimensions, localised fermions and gauge fields which propagate in the bulk. Such models naturally occur within the context of M theory. In SU(5) models we show that carefully including all such modes gives a distinctive pattern of decays through various channels including a strong suppression of decays into neutrinos or right handed positrons. By contrast there is no such suppression for SO(10). (author)

  5. Anderson localisation and optical-event horizons in rogue-soliton generation.

    Science.gov (United States)

    Saleh, Mohammed F; Conti, Claudio; Biancalana, Fabio

    2017-03-06

    We unveil the relation between the linear Anderson localisation process and nonlinear modulation instability. Anderson localised modes are formed in certain temporal intervals due to the random background noise. Such localised modes seed the formation of solitary waves that will appear during the modulation instability process at those preferred intervals. Afterwards, optical-event horizon effects between dispersive waves and solitons produce an artificial collective acceleration that favours the collision of solitons, which could eventually lead to a rogue-soliton generation.

  6. Graphene Oxide Nanoribbons Induce Autophagic Vacuoles in Neuroblastoma Cell Lines

    Directory of Open Access Journals (Sweden)

    Emanuela Mari

    2016-11-01

    Full Text Available Since graphene nanoparticles are attracting increasing interest in relation to medical applications, it is important to understand their potential effects on humans. In the present study, we prepared graphene oxide (GO nanoribbons by oxidative unzipping of single-wall carbon nanotubes (SWCNTs and analyzed their toxicity in two human neuroblastoma cell lines. Neuroblastoma is the most common solid neoplasia in children. The hallmark of these tumors is the high number of different clinical variables, ranging from highly metastatic, rapid progression and resistance to therapy to spontaneous regression or change into benign ganglioneuromas. Patients with neuroblastoma are grouped into different risk groups that are characterized by different prognosis and different clinical behavior. Relapse and mortality in high risk patients is very high in spite of new advances in chemotherapy. Cell lines, obtained from neuroblastomas have different genotypic and phenotypic features. The cell lines SK-N-BE(2 and SH-SY5Y have different genetic mutations and tumorigenicity. Cells were exposed to low doses of GO for different times in order to investigate whether GO was a good vehicle for biological molecules delivering individualized therapy. Cytotoxicity in both cell lines was studied by measuring cellular oxidative stress (ROS, mitochondria membrane potential, expression of lysosomial proteins and cell growth. GO uptake and cytoplasmic distribution of particles were studied by Transmission Electron Microscopy (TEM for up to 72 h. The results show that GO at low concentrations increased ROS production and induced autophagy in both neuroblastoma cell lines within a few hours of exposure, events that, however, are not followed by growth arrest or death. For this reason, we suggest that the GO nanoparticle can be used for therapeutic delivery to the brain tissue with minimal effects on healthy cells.

  7. TRANSANAL DRAINAGE OF ANASTOMOTIC LEAK FOLLOWING LOW ANTERIOR RESECTION- A NOVEL TECHNIQUE

    Directory of Open Access Journals (Sweden)

    Vinay Boppasamudra Nanjegowda

    2017-03-01

    Full Text Available BACKGROUND Anastomotic leaks after low anterior resection following rectal cancer is the major cause for morbidity and mortality. Various techniques for the conservative management of localised abscesses have been reported, but with variable results. Hence, in search of a new technique to treat anastomotic leak following low anterior resection, which is cost-effective and has good results. MATERIALS AND METHODS This study is a retrospective review of a prospectively maintained data of a novel technique to treat anastomotic leaks after low anterior resection with proximal diverting ileostomy in a single institution. RESULTS A total of 40 patients who underwent low anterior resection with diversion ileostomy for rectal cancer were studied. In them, 6 patients developed Grade B anastomotic leak, which were managed by this novel technique of paediatric endoscopic-guided transanal drainage of anastomotic leak following low anterior resection with diversion ileostomy using a 3-way Foley catheter. All the patients responded well, thus leading to local control of the septic foci without the need for any further radiological intervention or a laparotomy. This lead to salvaging the anastomosis. Out of the 6 patients managed by this technique, one patient developed stricture, which was managed by CRE balloon dilatation. All patients underwent stoma closure after a median postoperative time of 7 months. CONCLUSION Under paediatric endoscopic guidance, transanal drainage of anastomotic leak with an abscess cavity using a 3-way Foley catheter after low anterior resection with double-staple technique prevents further disruption of the anastomosis and local irrigation leads to faster sepsis control thus avoiding the morbidity of relaparotomy. This technique being a bedside procedure is cost-effective and feasible. This leads to good salvage of anastomosis along with early stoma closure and good long-term functional results.

  8. Olfactory neuroblastoma: 14-year experience at an Australian tertiary centre and the role for longer-term surveillance.

    Science.gov (United States)

    Schmidt, C; Potter, N; Porceddu, S; Panizza, B

    2017-07-01

    Olfactory neuroblastoma is a rare sinonasal malignancy, with poorly defined treatment protocols. Management at a tertiary centre was retrospectively evaluated to inform future treatment and follow up. Cases treated with curative intent (2000-2014) were included. Data were collected, and overall and disease-free survival rates were calculated. Eleven cases were identified, with a median follow up of 87 months. One patient was Kadish stage A, one was stage B, eight were stage C and one was stage D. The latter patient underwent chemoradiotherapy alone. The remaining patients proceeded to: endoscopic-assisted wide local excision (n = 2), anterior craniofacial resection (n = 4) or endoscopic craniofacial resection (n = 4). No patients had primary nodal disease or elective neck treatment. One patient had neoadjuvant chemoradiation. Six patients had post-operative radiotherapy; three received adjuvant chemotherapy. Two patients had late cervical node failure, and proceeded to neck dissection and post-operative radiotherapy. Two patients had late local recurrence. Ten-year overall and disease-free survival rates were 68.2 and 46.7 per cent, respectively. Longer-term follow up is supported given the incidence of late regional and local recurrence. Prophylactic treatment of cervical nodes in locally advanced disease is an area for further investigation.

  9. Laparoscopic resection of hilar cholangiocarcinoma.

    Science.gov (United States)

    Lee, Woohyung; Han, Ho-Seong; Yoon, Yoo-Seok; Cho, Jai Young; Choi, YoungRok; Shin, Hong Kyung; Jang, Jae Yool; Choi, Hanlim

    2015-10-01

    Laparoscopic resection of hilar cholangiocarcinoma is technically challenging because it involves complicated laparoscopic procedures that include laparoscopic hepatoduodenal lymphadenectomy, hemihepatectomy with caudate lobectomy, and hepaticojejunostomy. There are currently very few reports describing this type of surgery. Between August 2014 and December 2014, 5 patients underwent total laparoscopic or laparoscopic-assisted surgery for hilar cholangiocarcinoma. Two patients with type I or II hilar cholangiocarcinoma underwent radical hilar resection. Three patients with type IIIa or IIIb cholangiocarcinoma underwent extended hemihepatectomy together with caudate lobectomy. The median (range) age, operation time, blood loss, and length of hospital stay were 63 years (43-76 years), 610 minutes (410-665 minutes), 650 mL (450-1,300 mL), and 12 days (9-21 days), respectively. Four patients had a negative margin, but 1 patient was diagnosed with high-grade dysplasia on the proximal resection margin. The median tumor size was 3.0 cm. One patient experienced postoperative biliary leakage, which resolved spontaneously. Laparoscopic resection is a feasible surgical approach in selected patients with hilar cholangiocarcinoma.

  10. Awake craniotomy for tumor resection.

    Science.gov (United States)

    Attari, Mohammadali; Salimi, Sohrab

    2013-01-01

    Surgical treatment of brain tumors, especially those located in the eloquent areas such as anterior temporal, frontal lobes, language, memory areas, and near the motor cortex causes high risk of eloquent impairment. Awake craniotomy displays major rule for maximum resection of the tumor with minimum functional impairment of the Central Nervous System. These case reports discuss the use of awake craniotomy during the brain surgery in Alzahra Hospital, Isfahan, Iran. A 56-year-old woman with left-sided body hypoesthesia since last 3 months and a 25-year-old with severe headache of 1 month duration were operated under craniotomy for brain tumors resection. An awake craniotomy was planned to allow maximum tumor intraoperative testing for resection and neurologic morbidity avoidance. The method of anesthesia should offer sufficient analgesia, hemodynamic stability, sedation, respiratory function, and also awake and cooperative patient for different neurological test. Airway management is the most important part of anesthesia during awake craniotomy. Tumor surgery with awake craniotomy is a safe technique that allows maximal resection of lesions in close relationship to eloquent cortex and has a low risk of neurological deficit.

  11. Awake craniotomy for tumor resection

    Directory of Open Access Journals (Sweden)

    Mohammadali Attari

    2013-01-01

    Full Text Available Surgical treatment of brain tumors, especially those located in the eloquent areas such as anterior temporal, frontal lobes, language, memory areas, and near the motor cortex causes high risk of eloquent impairment. Awake craniotomy displays major rule for maximum resection of the tumor with minimum functional impairment of the Central Nervous System. These case reports discuss the use of awake craniotomy during the brain surgery in Alzahra Hospital, Isfahan, Iran. A 56-year-old woman with left-sided body hypoesthesia since last 3 months and a 25-year-old with severe headache of 1 month duration were operated under craniotomy for brain tumors resection. An awake craniotomy was planned to allow maximum tumor intraoperative testing for resection and neurologic morbidity avoidance. The method of anesthesia should offer sufficient analgesia, hemodynamic stability, sedation, respiratory function, and also awake and cooperative patient for different neurological test. Airway management is the most important part of anesthesia during awake craniotomy. Tumor surgery with awake craniotomy is a safe technique that allows maximal resection of lesions in close relationship to eloquent cortex and has a low risk of neurological deficit.

  12. Machine learning approach for single molecule localisation microscopy.

    Science.gov (United States)

    Colabrese, Silvia; Castello, Marco; Vicidomini, Giuseppe; Del Bue, Alessio

    2018-04-01

    Single molecule localisation (SML) microscopy is a fundamental tool for biological discoveries; it provides sub-diffraction spatial resolution images by detecting and localizing "all" the fluorescent molecules labeling the structure of interest. For this reason, the effective resolution of SML microscopy strictly depends on the algorithm used to detect and localize the single molecules from the series of microscopy frames. To adapt to the different imaging conditions that can occur in a SML experiment, all current localisation algorithms request, from the microscopy users, the choice of different parameters. This choice is not always easy and their wrong selection can lead to poor performance. Here we overcome this weakness with the use of machine learning. We propose a parameter-free pipeline for SML learning based on support vector machine (SVM). This strategy requires a short supervised training that consists in selecting by the user few fluorescent molecules (∼ 10-20) from the frames under analysis. The algorithm has been extensively tested on both synthetic and real acquisitions. Results are qualitatively and quantitatively consistent with the state of the art in SML microscopy and demonstrate that the introduction of machine learning can lead to a new class of algorithms competitive and conceived from the user point of view.

  13. Investigation into Generation of Micro Features by Localised Electrochemical Deposition

    Science.gov (United States)

    Debnath, Subhrajit; Laskar, Hanimur Rahaman; Bhattacharyya, B.

    2017-11-01

    With the fast advancement of technology, localised electrochemical deposition (LECD) is becoming very advantageous in generating high aspect ratio micro features to meet the steep demand in modern precision industries of the present world. Except many other advantages, this technology is highly uncomplicated and economical for fabricating metal micro-parts with in micron ranges. In the present study, copper micro-columns have been fabricated utilizing LECD process. Different process parameters such as voltage, frequency, duty ratio and electrolyte concentration, which affect the deposition performance have been identified and their effects on deposition performances such as deposition rate, height and diameter of the micro-columns have been experimentally investigated. Taguchi's methodology has been used to study the effects as well as to obtain the optimum values of process parameters so that localised deposition with best performance can be achieved. Moreover, the generated micro-columns were carefully observed under optical and scanning electron microscope from where the surface quality of the deposited micro-columns has been studied qualitatively. Also, an array of copper micro-columns has been fabricated on stainless steel (SS-304) substrate for further exploration of LECD process capability.

  14. Laparoscopic resection for diverticular disease.

    Science.gov (United States)

    Bruce, C J; Coller, J A; Murray, J J; Schoetz, D J; Roberts, P L; Rusin, L C

    1996-10-01

    The role of laparoscopic surgery in treatment of patients with diverticulitis is unclear. A retrospective comparison of laparoscopic with conventional surgery for patients with chronic diverticulitis was performed to assess morbidity, recovery from surgery, and cost. Records of patients undergoing elective resection for uncomplicated diverticulitis from 1992 to 1994 at a single institution were reviewed. Laparoscopic resection involved complete intracorporeal dissection, bowel division, and anastomosis with extracorporeal placement of an anvil. Sigmoid and left colon resections were performed laparoscopically in 25 patients and by open technique in 17 patients by two independent operating teams. No significant differences existed in age, gender, weight, comorbidities, or operations performed. In the laparoscopic group, three operations were converted to open laparotomy (12 percent) because of unclear anatomy. Major complications occurred in two patients who underwent laparoscopic resection, both requiring laparotomy, and in one patient in the conventional surgery group who underwent computed tomographic-guided drainage of an abscess. Patients who underwent laparoscopic resection tolerated a regular diet sooner than patients who underwent conventional surgery (3.2 +/- 0.9 vs. 5.7 +/- 1.1 days; P < 0.001) and were discharged from the hospital earlier (4.2 +/- 1.1 vs. 6.8 +/- 1.1 days; P < 0.001). Overall costs were higher in the laparoscopic group than the open surgery group ($10,230 +/- 49.1 vs. $7,068 +/- 37.1; P < 0.001) because of a significantly longer total operating room time (397 +/- 9.1 vs. 115 +/- 5.1 min; P < 0.001). Follow-up studies with a mean of one year revealed two port site infections in the laparoscopic group and one wound infection in the open group. Of patients undergoing conventional resection, one patient experienced a postoperative bowel obstruction that was managed nonoperatively, and, in one patient, an incarcerated incisional hernia

  15. Identification of GPC2 as an Oncoprotein and Candidate Immunotherapeutic Target in High-Risk Neuroblastoma.

    Science.gov (United States)

    Bosse, Kristopher R; Raman, Pichai; Zhu, Zhongyu; Lane, Maria; Martinez, Daniel; Heitzeneder, Sabine; Rathi, Komal S; Kendsersky, Nathan M; Randall, Michael; Donovan, Laura; Morrissy, Sorana; Sussman, Robyn T; Zhelev, Doncho V; Feng, Yang; Wang, Yanping; Hwang, Jennifer; Lopez, Gonzalo; Harenza, Jo Lynne; Wei, Jun S; Pawel, Bruce; Bhatti, Tricia; Santi, Mariarita; Ganguly, Arupa; Khan, Javed; Marra, Marco A; Taylor, Michael D; Dimitrov, Dimiter S; Mackall, Crystal L; Maris, John M

    2017-09-11

    We developed an RNA-sequencing-based pipeline to discover differentially expressed cell-surface molecules in neuroblastoma that meet criteria for optimal immunotherapeutic target safety and efficacy. Here, we show that GPC2 is a strong candidate immunotherapeutic target in this childhood cancer. We demonstrate high GPC2 expression in neuroblastoma due to MYCN transcriptional activation and/or somatic gain of the GPC2 locus. We confirm GPC2 to be highly expressed on most neuroblastomas, but not detectable at appreciable levels in normal childhood tissues. In addition, we demonstrate that GPC2 is required for neuroblastoma proliferation. Finally, we develop a GPC2-directed antibody-drug conjugate that is potently cytotoxic to GPC2-expressing neuroblastoma cells. Collectively, these findings validate GPC2 as a non-mutated neuroblastoma oncoprotein and candidate immunotherapeutic target. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Augmented reality in bone tumour resection

    Science.gov (United States)

    Park, Y. K.; Gupta, S.; Yoon, C.; Han, I.; Kim, H-S.; Choi, H.; Hong, J.

    2017-01-01

    Objectives We evaluated the accuracy of augmented reality (AR)-based navigation assistance through simulation of bone tumours in a pig femur model. Methods We developed an AR-based navigation system for bone tumour resection, which could be used on a tablet PC. To simulate a bone tumour in the pig femur, a cortical window was made in the diaphysis and bone cement was inserted. A total of 133 pig femurs were used and tumour resection was simulated with AR-assisted resection (164 resection in 82 femurs, half by an orthropaedic oncology expert and half by an orthopaedic resident) and resection with the conventional method (82 resection in 41 femurs). In the conventional group, resection was performed after measuring the distance from the edge of the condyle to the expected resection margin with a ruler as per routine clinical practice. Results The mean error of 164 resections in 82 femurs in the AR group was 1.71 mm (0 to 6). The mean error of 82 resections in 41 femurs in the conventional resection group was 2.64 mm (0 to 11) (p Augmented reality in bone tumour resection: An experimental study. Bone Joint Res 2017;6:137–143. PMID:28258117

  17. Localisation of RNAs into the germ plasm of vitellogenic Xenopus oocytes.

    Directory of Open Access Journals (Sweden)

    Sarbjit Nijjar

    Full Text Available We have studied the localisation of mRNAs in full-grown Xenopus laevis oocytes by injecting fluorescent RNAs, followed by confocal microscopy of the oocyte cortex. Concentrating on RNA encoding the Xenopus Nanos homologue, nanos1 (formerly Xcat2, we find that it consistently localised into aggregated germ plasm ribonucleoprotein (RNP particles, independently of cytoskeletal integrity. This implies that a diffusion/entrapment-mediated mechanism is active, as previously reported for previtellogenic oocytes. Sometimes this was accompanied by localisation into scattered particles of the "late", Vg1/VegT pathway; occasionally only late pathway localisation was seen. The Xpat RNA behaved in an identical fashion and for neither RNA was the localisation changed by any culture conditions tested. The identity of the labelled RNP aggregates as definitive germ plasm was confirmed by their inclusion of abundant mitochondria and co-localisation with the germ plasm protein Hermes. Further, the nanos1/Hermes RNP particles are interspersed with those containing the germ plasm protein Xpat. These aggregates may be followed into the germ plasm of unfertilized eggs, but with a notable reduction in its quantity, both in terms of injected molecules and endogenous structures. Our results conflict with previous reports that there is no RNA localisation in large oocytes, and that during mid-oogenesis even germ plasm RNAs localise exclusively by the late pathway. We find that in mid oogenesis nanos1 RNA also localises to germ plasm but also by the late pathway. Late pathway RNAs, Vg1 and VegT, also may localise into germ plasm. Our results support the view that mechanistically the two modes of localisation are extremely similar, and that in an injection experiment RNAs might utilise either pathway, the distinction in fates being very subtle and subject to variation. We discuss these results in relation to their biological significance and the results of others.

  18. Ras-MAPK signaling in differentiating SH-SY5Y human neuroblastoma cells

    OpenAIRE

    Olsson, Anna-Karin

    2000-01-01

    Neuroblastoma is a malignant childhood cancer, originating from sympathetic neuroblasts of the peripheral nervous system. Neuroblastoma is a heterogenous group of tumours, while some are highly malignant others can spontaneosly mature into a more benign form or regress. Less than half of the patients survive and this statistics has improved only modestly over the past 20 years. SH-SY5Y is a human neuroblastoma cell line established from a highly malignant tumour. The cells have retained a ca...

  19. Bilateral adrenal cystic neuroblastoma with superior vena cava syndrome and massive intracystic haemorrhage

    International Nuclear Information System (INIS)

    Pinarli, Faruk Guclu; Danaci, Murat; Diren, Baris; Tander, Burak; Rizalar, Riza; Dagdemir, Ayhan; Acar, Sabri

    2004-01-01

    Bilateral cystic adrenal tumours are a rare presentation of neuroblastoma. Intratumoural haemorrhage is a frequent finding in neuroblastoma, but is rarely symptomatic. We present an 11-month-old girl with predominantly cystic bilateral neuroblastomas and distant lymph-node metastasis. Massive intracystic haemorrhage and superior vena cava (SVC) syndrome were ominous prognostic factors, leading to death. Large tumours with intracystic haemorrhage might require a conservative approach. (orig.)

  20. PI3K/AKT and ERK regulate retinoic acid-induced neuroblastoma cellular differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Qiao, Jingbo [Department of Pediatric Surgery, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Paul, Pritha; Lee, Sora [Department of Pediatric Surgery, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Qiao, Lan; Josifi, Erlena; Tiao, Joshua R. [Department of Pediatric Surgery, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Chung, Dai H., E-mail: dai.chung@vanderbilt.edu [Department of Pediatric Surgery, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, TN 37232 (United States)

    2012-08-03

    Highlights: Black-Right-Pointing-Pointer Retinoic acid (RA) induces neuroblastoma cells differentiation, which is accompanied by G0/G1 cell cycle arrest. Black-Right-Pointing-Pointer RA resulted in neuroblastoma cell survival and inhibition of DNA fragmentation; this is regulated by PI3K pathway. Black-Right-Pointing-Pointer RA activates PI3K and ERK1/2 pathway; PI3K pathway mediates RA-induced neuroblastoma cell differentiation. Black-Right-Pointing-Pointer Upregulation of p21 is necessary for RA-induced neuroblastoma cell differentiation. -- Abstract: Neuroblastoma, the most common extra-cranial solid tumor in infants and children, is characterized by a high rate of spontaneous remissions in infancy. Retinoic acid (RA) has been known to induce neuroblastoma differentiation; however, the molecular mechanisms and signaling pathways that are responsible for RA-mediated neuroblastoma cell differentiation remain unclear. Here, we sought to determine the cell signaling processes involved in RA-induced cellular differentiation. Upon RA administration, human neuroblastoma cell lines, SK-N-SH and BE(2)-C, demonstrated neurite extensions, which is an indicator of neuronal cell differentiation. Moreover, cell cycle arrest occurred in G1/G0 phase. The protein levels of cyclin-dependent kinase inhibitors, p21 and p27{sup Kip}, which inhibit cell proliferation by blocking cell cycle progression at G1/S phase, increased after RA treatment. Interestingly, RA promoted cell survival during the differentiation process, hence suggesting a potential mechanism for neuroblastoma resistance to RA therapy. Importantly, we found that the PI3K/AKT pathway is required for RA-induced neuroblastoma cell differentiation. Our results elucidated the molecular mechanism of RA-induced neuroblastoma cellular differentiation, which may be important for developing novel therapeutic strategy against poorly differentiated neuroblastoma.

  1. Omega-3 fatty acid supplementation delays the progression of neuroblastoma in vivo.

    Science.gov (United States)

    Gleissman, Helena; Segerström, Lova; Hamberg, Mats; Ponthan, Frida; Lindskog, Magnus; Johnsen, John Inge; Kogner, Per

    2011-04-01

    Epidemiological and preclinical studies have revealed that omega-3 fatty acids have anticancer properties. We have previously shown that the omega-3 fatty acid docosahexaenoic acid (DHA) induces apoptosis of neuroblastoma cells in vitro by mechanisms involving intracellular peroxidation of DHA by means of 15-lipoxygenase or autoxidation. In our study, the effects of DHA supplementation on neuroblastoma tumor growth in vivo were investigated using two complementary approaches. For the purpose of prevention, DHA as a dietary supplement was fed to athymic rats before the rats were xenografted with human neuroblastoma cells. For therapeutic purposes, athymic rats with established neuroblastoma xenografts were given DHA daily by gavage and tumor growth was monitored. DHA levels in plasma and tumor tissue were analyzed by gas liquid chromatography. DHA delayed neuroblastoma xenograft development and inhibited the growth of established neuroblastoma xenografts in athymic rats. A revised version of the Pediatric Preclinical Testing Program evaluation scheme used as a measurement of treatment response showed that untreated control animals developed progressive disease, whereas treatment with DHA resulted in stable disease or partial response, depending on the DHA concentration. In conclusion, prophylactic treatment with DHA delayed neuroblastoma development, suggesting that DHA could be a potential agent in the treatment of minimal residual disease and should be considered for prevention in selected cases. Treatment results on established aggressive neuroblastoma tumors suggest further studies aiming at a clinical application in children with high-risk neuroblastoma. Copyright © 2010 UICC.

  2. Computed tomography as a supplement to urography in the evaluation of suspected neuroblastoma

    International Nuclear Information System (INIS)

    Siegel, M. J.; Sagel, S.S.

    1982-01-01

    Eleven children in whom a retropertioneal neuroblastoma was suspected on the basis of plain radiographic or urographic findings underwent computed tomography (CT). CT identified and localized a neurogenic tumor in eight patients. Calcifications were demonstrated by CT in six lesions, but by urography in only four. One neuroblastoma detected by CT was not seen on the urogram; in five patients greater extent of the tumor was defined by CT than by conventional radiologic procedures. In three patients CT excluded a neuroblastoma, but diagnosed other disorders (hepatic tumor, pancreatitis, and retrocaval ureter). Our results confirm that CT is a simple and accurate method for diagnosis, delineation of extent, or exclusion of neuroblastoma

  3. Novel targeted therapy for neuroblastoma: silencing the MXD3 gene using siRNA.

    Science.gov (United States)

    Duong, Connie; Yoshida, Sakiko; Chen, Cathy; Barisone, Gustavo; Diaz, Elva; Li, Yueju; Beckett, Laurel; Chung, Jong; Antony, Reuben; Nolta, Jan; Nitin, Nitin; Satake, Noriko

    2017-09-01

    BackgroundNeuroblastoma is the second most common extracranial cancer in children. Current therapies for neuroblastoma, which use a combination of chemotherapy drugs, have limitations for high-risk subtypes and can cause significant long-term adverse effects in young patients. Therefore, a new therapy is needed. In this study, we investigated the transcription factor MXD3 as a potential therapeutic target in neuroblastoma.MethodsMXD3 expression was analyzed in five neuroblastoma cell lines by immunocytochemistry and quantitative real-time reverse transcription PCR, and in 18 primary patient tumor samples by immunohistochemistry. We developed nanocomplexes using siRNA and superparamagnetic iron oxide nanoparticles to target MXD3 in neuroblastoma cell lines in vitro as a single-agent therapeutic and in combination with doxorubicin, vincristine, cisplatin, or maphosphamide-common drugs used in current neuroblastoma treatment.ResultsMXD3 was highly expressed in neuroblastoma cell lines and in patient tumors that had high-risk features. Neuroblastoma cells treated in vitro with the MXD3 siRNA nanocomplexes showed MXD3 protein knockdown and resulted in cell apoptosis. Furthermore, on combining MXD3 siRNA nanocomplexes with each of the four drugs, all showed additive efficacy.ConclusionThese results indicate that MXD3 is a potential new target and that the use of MXD3 siRNA nanocomplexes is a novel therapeutic approach for neuroblastoma.

  4. Abnormal brain MRI in a case of acute ataxia as the only sign of abdominal neuroblastoma

    International Nuclear Information System (INIS)

    Molla Mohammadi, M.; Karimzadeh, P.; Khatami, A.; Jadali, F.

    2010-01-01

    Ataxia is a movement disorder that may manifest an acute, intermittent, non progressive or chronic progressive course. Ataxia alone is rare as a para neoplastic sign, especially if it is due to neuroblastoma (abdominal or chest). We report an abdominal neuroblastoma in a two-year-old girl presenting with only acute ataxia and abnormal neuroimaging. Brain MRI showed abnormal signal finding in the medulla, pons, cortico spinal tract and the periventricular space. In the abdominal CT, a mass was detected in the right adrenal gland with calcification and the histopathologic examination re-vealed neuroblastoma. We suggest in children with acute ataxia, with or without opalescence-myoclonus, neuroblastoma should be considered.

  5. The importance of strain localisation in shear zones

    Science.gov (United States)

    Bons, Paul D.; Finch, Melanie; Gomez-Rivas, Enrique; Griera, Albert; Llorens, Maria-Gema; Steinbach, Florian; Weikusat, Ilka

    2016-04-01

    The occurrence of various types of shear bands (C, C', C'') in shear zones indicate that heterogeneity of strain is common in strongly deformed rocks. However, the importance of strain localisation is difficult to ascertain if suitable strain markers are lacking, which is usually the case. Numerical modelling with the finite-element method has so far not given much insight in the development of shear bands. We suggest that this is not only because the modelled strains are often not high enough, but also because this technique (that usually assumes isotropic material properties within elements) does not properly incorporate mineral deformation behaviour. We simulated high-strain, simple-shear deformation in single- and polyphase materials with a full-field theory (FFT) model coupled to the Elle modelling platform (www.elle.ws; Lebensohn 2001; Bons et al. 2008). The FFT-approach simulates visco-plastic deformation by dislocation glide, taking into account the different available slip systems and their critical resolved shear stresses in relations to the applied stresses. Griera et al. (2011; 2013) have shown that this approach is particularly well suited for strongly anisotropic minerals, such as mica and ice Ih (Llorens 2015). We modelled single- and polyphase composites of minerals with different anisotropies and strengths, roughly equivalent to minerals such as ice Ih, mica, quartz and feldspar. Single-phase polycrystalline aggregates show distinct heterogeneity of strain rate, especially in case of ice Ih, which is mechanically close to mica (see also Griera et al. 2015). Finite strain distributions are heterogeneous as well, but the patterns may differ from that of the strain rate distribution. Dynamic recrystallisation, however, usually masks any strain and strain rate localisation (Llorens 2015). In case of polyphase aggregates, equivalent to e.g. a granite, we observe extensive localisation in both syn- and antithetic shear bands. The antithetic shear bands

  6. Evaluating ALWadHA for providing secure localisation for wireless sensor networks

    CSIR Research Space (South Africa)

    Abu-Mahfouz, Adnan M

    2013-09-01

    Full Text Available secure localisation algorithms that are able to work in a hostile environment. An attacker could compromise, or masquerade as, a beacon node and send incorrect location information. Localisation in a hostile environment is a critical problem in wireless...

  7. Neuroglobin in the rat brain (II): co-localisation with neurotransmitters

    DEFF Research Database (Denmark)

    Hundahl, Christian Ansgar; Kelsen, Jesper; Dewilde, Sylvia

    2008-01-01

    In an accompanying article, we found that neuroglobin (Ngb) was expressed in a few well-defined nuclei in the rat brain. Here, we show by use of immunohistochemistry and in situ hybridisation (ISH) that Ngb co-localise with several specific neurotransmitters. Ngb co-localise consistently with tyr...

  8. [Robot-assisted pancreatic resection].

    Science.gov (United States)

    Müssle, B; Distler, M; Weitz, J; Welsch, T

    2017-06-01

    Although robot-assisted pancreatic surgery has been considered critically in the past, it is nowadays an established standard technique in some centers, for distal pancreatectomy and pancreatic head resection. Compared with the laparoscopic approach, the use of robot-assisted surgery seems to be advantageous for acquiring the skills for pancreatic, bile duct and vascular anastomoses during pancreatic head resection and total pancreatectomy. On the other hand, the use of the robot is associated with increased costs and only highly effective and professional robotic programs in centers for pancreatic surgery will achieve top surgical and oncological quality, acceptable operation times and a reduction in duration of hospital stay. Moreover, new technologies, such as intraoperative fluorescence guidance and augmented reality will define additional indications for robot-assisted pancreatic surgery.

  9. Enhanced recovery after esophageal resection.

    Science.gov (United States)

    Vorwald, Peter; Bruna Esteban, Marcos; Ortega Lucea, Sonia; Ramírez Rodríguez, Jose Manuel

    2018-03-21

    ERAS is a multimodal perioperative care program which replaces traditional practices concerning analgesia, intravenous fluids, nutrition, mobilization as well as a number of other perioperative items, whose implementation is supported by evidence-based best practices. According to the RICA guidelines published in 2015, a review of the literature and the consensus established at a multidisciplinary meeting in 2015, we present a protocol that contains the basic procedures of an ERAS pathway for resective esophageal surgery. The measures involved in this ERAS pathway are structured into 3areas: preoperative, perioperative and postoperative. The consensus document integrates all the analyzed items in a unique time chart. ERAS programs in esophageal resection surgery can reduce postoperative morbidity, mortality, hospitalization and hospital costs. Copyright © 2018 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

  10. Localisation of metastatic carcinoma by a radiolabelled monoclonal antibody

    Energy Technology Data Exchange (ETDEWEB)

    Smedley, H M; Ritson, A; Wraight, P; Sikora, K [Addenbrooke' s Hospital, Cambridge (UK); Hinchingbrooke Hospital, Huntingdon (UK)); Finan, P [St. James Hospital, Leeds (UK); Lennox, E S; Takei, F [Medical Research Council, Cambridge (UK)

    1983-02-01

    Rat monoclonal antibodies were prepared by immunising rats with human colorectal carcinoma cell membranes and fusing splenic lymphocytes with a rat myeloma. Hybridoma supernatants were screened by binding assays on membranes prepared from colorectal carcinoma tissue. One hybridoma supernatant, containing a monoclonal antibody with high binding activity on malignant compared to normal colon sections, was grown in large quantities in serum-free medium. After ammonium sulphate precipitation the antibody was purified by ion-exchange chromatography and labelled with /sup 131/I. Radiolabelled antibody was administered i.v. to 27 patients with colonic and other tumours. Scintigrams were obtained at 48 h. Computerised subtraction of the blood pool image revealed localised areas of uptake corresponding with areas of known disease in 13/16 patients with colorectal carcinoma and 3/4 patients with breast cancer.

  11. Passive RFID Localisation Framework in Smart Homes Healthcare Settings.

    Science.gov (United States)

    Alsinglawi, Belal; Liu, Tony; Nguyen, Quang Vinh; Gunawardana, Upul; Maeder, Anthony; Simoff, Simeon

    2016-01-01

    In recent years, Smart Homes have become a solution to benefit impaired individuals and elderly in their daily life settings. In healthcare applications, pervasive technologies have enabled the practicality of personal monitoring using Indoor positioning technologies. Radio-Frequency Identification (RFID) is a promising technology, which is useful for non-invasive tracking of activities of daily living. Many implementations have focused on using battery-enabled tags like in RFID active tags, which require frequent maintenance and they are costly. Other systems can use wearable sensors requiring individuals to wear tags which may be inappropriate for elders. Successful implementations of a tracking system are dependent on multiple considerations beyond the physical performance of the solution, such as affordability and human acceptance. This paper presents a localisation framework using passive RFID sensors. It aims to provide a low cost solution for subject location in Smart Homes healthcare.

  12. Active surveillance strategy for patients with localised prostate cancer

    DEFF Research Database (Denmark)

    Thomsen, Frederik Birkebæk

    2014-01-01

    BACKGROUND: Active surveillance - an initial observational strategy - offers a tailored management of patients with localised prostate cancer. The aim of the strategy is to appoint patients with potentially lethal prostate cancer to curatively intended treatment, while patients with slowly evolving...... measurements, repeated biopsies, and regular digital rectal examinations. The programme recommended change of management from active surveillance to curatively intended treatment based on PSA doubling time, deteriorating histopathology in repeated prostatic biopsies, and increased clinical tumour category...... with defined final histopathological findings at radical prostatectomy that was perceived as unacceptable for a continued observational strategy. CONCLUSION: The thesis has demonstrated that active surveillance is feasible and reduces the number of patients undergoing curative intended treatment. However...

  13. Dark matter and localised fermions from spherical orbifolds?

    Energy Technology Data Exchange (ETDEWEB)

    Cacciapaglia, Giacomo; Deandrea, Aldo [Université de Lyon,Lyon (France); Université Lyon 1, CNRS/IN2P3, UMR5822 IPNL,F-69622 Villeurbanne Cedex (France); Deutschmann, Nicolas [Université de Lyon,Lyon (France); Université Lyon 1, CNRS/IN2P3, UMR5822 IPNL,F-69622 Villeurbanne Cedex (France); Centre for Cosmology, Particle Physics and Phenomenology (CP3),Université catholique de Louvain,Chemin du Cyclotron 2, B-1348 Louvain-la-Neuve (Belgium)

    2016-04-14

    We study a class of six-dimensional models based on positive curvature surfaces (spherical 2-orbifolds) as extra-spaces. Using the Newman-Penrose formalism, we discuss the particle spectrum in this class of models. The fermion spectrum problem, which has been addressed with flux compactifications in the past, can be avoided using localised fermions. In this framework, we find that there are four types of geometry compatible with the existence of a stable dark matter candidate and we study the simplest case in detail. Using the complementarity between collider resonance searches and relic density constraints, we show that this class of models is under tension, unless the model lies in a funnel region characterised by a resonant Higgs s-channel in the dark matter annihilation.

  14. Østebø, Terje. — Localising Salafism

    OpenAIRE

    Vezzadini, Elena

    2012-01-01

    Localising Salafism est une étude approfondie sur l’origine et le développement du salafisme dans le Bale, une province au sud-est de l’Éthiopie, habitée majoritairement par les Oromo qui y constituent environ 90 % de la population. il s’agit aussi d’une région à grande majorité musulmane (92 %), qui fait partie des neuf divisions administratives de l’Éthiopie, connue comme Oromiyaa. L’auteur travaille donc sur une région très peu étudiée, et sur un sujet, l’islam en Éthiopie, encore marginal...

  15. Globally reasoning about localised security policies in distributed systems

    DEFF Research Database (Denmark)

    Hernandez, Alejandro Mario

    In this report, we aim at establishing proper ways for model checking the global security of distributed systems, which are designed consisting of set of localised security policies that enforce specific issues about the security expected. The systems are formally specified following a syntax......, defined in detail in this report, and their behaviour is clearly established by the Semantics, also defined in detail in this report. The systems include the formal attachment of security policies into their locations, whose intended interactions are trapped by the policies, aiming at taking access...... control decisions of the system, and the Semantics also takes care of this. Using the Semantics, a Labelled Transition System (LTS) can be induced for every particular system, and over this LTS some model checking tasks could be done. We identify how this LTS is indeed obtained, and propose an alternative...

  16. Awake craniotomy for tumor resection

    OpenAIRE

    Mohammadali Attari; Sohrab Salimi

    2013-01-01

    Surgical treatment of brain tumors, especially those located in the eloquent areas such as anterior temporal, frontal lobes, language, memory areas, and near the motor cortex causes high risk of eloquent impairment. Awake craniotomy displays major rule for maximum resection of the tumor with minimum functional impairment of the Central Nervous System. These case reports discuss the use of awake craniotomy during the brain surgery in Alzahra Hospital, Isfahan, Iran. A 56-year-old woman with le...

  17. Nucleolar protein PES1 is a marker of neuroblastoma outcome and is associated with neuroblastoma differentiation

    Science.gov (United States)

    Nakaguro, Masato; Kiyonari, Shinichi; Kishida, Satoshi; Cao, Dongliang; Murakami-Tonami, Yuko; Ichikawa, Hitoshi; Takeuchi, Ichiro; Nakamura, Shigeo; Kadomatsu, Kenji

    2015-01-01

    Neuroblastoma (NB) is a childhood malignant tumor that arises from precursor cells of the sympathetic nervous system. Spontaneous regression is a phenomenon unique to NBs and is caused by differentiation of tumor cells. PES1 is a multifunctional protein with roles in both neural development and ribosome biogenesis. Various kinds of models have revealed the significance of PES1 in neurodevelopment. However, the roles of PES1 in NB tumorigenesis and differentiation have remained unknown. Here we show that NB cases with MYCN amplification and clinically unfavorable stage (INSS stage 4) express higher levels of PES1. High PES1 expression was associated with worse overall and relapse-free survival. In NB cell lines, PES1 knockdown suppressed tumor cell growth and induced apoptosis. This growth inhibition was associated with the expression of NB differentiation markers. However, when the differentiation of NB cell lines was induced by the use of all-trans retinoic acid, there was a corresponding decrease in PES1 expression. Pes1 expression of tumorspheres originated from MYCN transgenic mice also diminished after the induction of differentiation with growth factors. We also reanalyzed the distribution of PES1 in the nucleolus. PES1 was localized in the dense fibrillar component, but not in the granular component of nucleoli. After treatment with the DNA-damaging agent camptothecin, this distribution was dramatically changed to diffuse nucleoplasmic. These data suggest that PES1 is a marker of NB outcome, that it regulates NB cell proliferation, and is associated with NB differentiation. PMID:25557119

  18. 3D Image Fusion to Localise Intercostal Arteries During TEVAR

    Directory of Open Access Journals (Sweden)

    G. Koutouzi

    Full Text Available Purpose: Preservation of intercostal arteries during thoracic aortic procedures reduces the risk of post-operative paraparesis. The origins of the intercostal arteries are visible on pre-operative computed tomography angiography (CTA, but rarely on intra-operative angiography. The purpose of this report is to suggest an image fusion technique for intra-operative localisation of the intercostal arteries during thoracic endovascular repair (TEVAR. Technique: The ostia of the intercostal arteries are identified and manually marked with rings on the pre-operative CTA. The optimal distal landing site in the descending aorta is determined and marked, allowing enough length for an adequate seal and attachment without covering more intercostal arteries than necessary. After 3D/3D fusion of the pre-operative CTA with an intra-operative cone-beam CT (CBCT, the markings are overlaid on the live fluoroscopy screen for guidance. The accuracy of the overlay is confirmed with digital subtraction angiography (DSA and the overlay is adjusted when needed. Stent graft deployment is guided by the markings. The initial experience of this technique in seven patients is presented. Results: 3D image fusion was feasible in all cases. Follow-up CTA after 1 month revealed that all intercostal arteries planned for preservation, were patent. None of the patients developed signs of spinal cord ischaemia. Conclusion: 3D image fusion can be used to localise the intercostal arteries during TEVAR. This may preserve some intercostal arteries and reduce the risk of post-operative spinal cord ischaemia. Keywords: TEVAR, Intercostal artery, Spinal cord ischaemia, 3D image fusion, Image guidance, Cone-beam CT

  19. Localisation and mechanism of renal retention of radiolabelled somatostatin analogues

    Energy Technology Data Exchange (ETDEWEB)

    Melis, Marleen; Krenning, Eric P.; Bernard, Bert F.; Jong, Marion de [Erasmus MC, Department of Nuclear Medicine, Rotterdam (Netherlands); Barone, Raffaella [UCL, Centre of Nuclear Medicine and Laboratory of PET, Brussels (Belgium); Visser, Theo J. [Erasmus MC, Department of Internal Medicine, Rotterdam (Netherlands)

    2005-10-01

    Radiolabelled somatostatin analogues, such as octreotide and octreotate, are used for tumour scintigraphy and radionuclide therapy. The kidney is the most important critical organ during such therapy owing to the reabsorption and retention of radiolabelled peptides. The aim of this study was to investigate in a rat model both the localisation and the mechanism of renal uptake after intravenous injection of radiolabelled somatostatin analogues. The multi-ligand megalin/cubilin receptor complex, responsible for reabsorption of many peptides and proteins in the kidney, is an interesting candidate for renal endocytosis of these peptide analogues. For localisation studies, ex vivo autoradiography and micro-autoradiography of rat kidneys were performed 1-24 h after injection of radiolabelled somatostatin analogues and compared with the renal anti-megalin immunohistochemical staining pattern. To confirm a role of megalin in the mechanism of renal retention of [{sup 111}In-DTPA]octreotide, the effects of three inhibitory substances were explored in rats. Renal ex vivo autoradiography showed high cortical radioactivity and lower radioactivity in the outer medulla. The distribution of cortical radioactivity was inhomogeneous. Micro-autoradiography indicated that radioactivity was only retained in the proximal tubules. The anti-megalin immunohistochemical staining pattern showed a strong similarity with the renal [{sup 111}In-DTPA]octreotide ex vivo autoradiograms. Biodistribution studies showed that co-injection of positively charged d-lysine reduced renal uptake to 60% of control. Sodium maleate reduced renal [{sup 111}In-DTPA]octreotide uptake to 15% of control. Finally, cisplatin pre-treatment of rats reduced kidney uptake to 70% of control. Renal retention of [{sup 111}In-DTPA]octreotide is confined to proximal tubules in the rat kidney, in which megalin-mediated endocytosis may play an important part. (orig.)

  20. Localised states in organic semiconductors and their detection

    Science.gov (United States)

    Imperia, Paolo

    2002-06-01

    New polymers and low molecular compounds, suitable for organic light emitting devices and organic electronic applications, have been synthesised in this years in order to obtain electron transport characteristics compatible with requirements for applications in real plastic devices. However, despite of the technological importance and of the relevant progress in devices manufacture, fundamental physical properties of such class of materials are still not enough studied. In particular extensive presence of distributions of localised states inside the band gap has a deep impact on their electronic properties. Such presence of shallow traps as well as the influence of the sample preparation conditions on deep and shallow localised states have not been, until now, systematically explored. The thermal techniques are powerful tools in order to study localised levels in inorganic and organic materials. Thermally stimulated luminescence (TSL), thermally stimulated currents (TSC) and thermally stimulated depolarisation currents (TSDC) allow to deeply look to shallow and deep trap levels as well as they permit to study, in synergy with dielectric spectroscopy (DES), polarisation and depolarisation effects. We studied, by means of numerical simulations, the first and the second order kinetic equations characterised by negligible and strong re-trapping respectively. We included in the equations Gaussian, exponential and quasi-continuous distributions of localised states. The shapes of the theoretical peaks have been investigated by means of systematic variation of the two main parameters of the equations, i. e. the energy trap depth E and the frequency factor a and of the parameters regulating the distributions, in particular for a Gaussian distribution the distribution width s and the integration limits. The theoretical findings have been applied to experimental glow curves. Thin films of polymers and low molecular compounds. Polyphenylquinoxalines, trisphenylquinoxalines and

  1. A 6-gene signature identifies four molecular subgroups of neuroblastoma

    OpenAIRE

    Abel, Frida; Dalevi, Daniel; Nethander, Maria; Jörnsten, Rebecka; De Preter, Katleen; Vermeulen, Joëlle; Stallings, Raymond; Kogner, Per; Maris, John; Nilsson, Staffan

    2011-01-01

    Abstract Background There are currently three postulated genomic subtypes of the childhood tumour neuroblastoma (NB); Type 1, Type 2A, and Type 2B. The most aggressive forms of NB are characterized by amplification of the oncogene MYCN (MNA) and low expression of the favourable marker NTRK1. Recently, mutations or high expression of the familial predisposition gene Anaplastic Lymphoma Kinase (ALK) was associated to unfavourable biology of sporadic NB. Also, various other genes have been linke...

  2. Ultra-high Density SNParray in Neuroblastoma Molecular Diagnostics

    Directory of Open Access Journals (Sweden)

    Inge M. Ambros

    2014-08-01

    Full Text Available Neuroblastoma serves as a paradigm for applying tumor genomic data for determining patient prognosis and thus for treatment allocation. MYCN status, i.e. amplified vs. non-amplified, was one of the very first biomarkers in oncology to discriminate aggressive from less aggressive or even favorable clinical courses of neuroblastoma. However, MYCN amplification is by far not the only genetic change associated with unfavorable clinical courses: so called segmental chromosomal aberrations, i.e. gains or losses of chromosomal fragments, can also indicate tumor aggressiveness. The clinical use of these genomic aberrations has, however, been hampered for many years by methodical and interpretational problems. Only after reaching worldwide consensus on markers, methodology, and data interpretation, information on SCAs has recently been implemented in clinical studies. Now, a number of collaborative studies within COG, GPOH and SIOPEN use genomic information to stratify therapy for patients with localized and metastatic disease. Recently, new types of DNA based aberrations influencing the clinical behavior of neuroblastomas have been described. Deletions or mutations of genes like ATRX and a phenomenon referred to as chromothripsis are all assumed to correlate with an unfavorable clinical behavior. However, these genomic aberrations need to be scrutinized in larger studies applying the most appropriate techniques. Single nucleotide polymorphism (SNP arrays have proven successful in deciphering genomic aberrations of cancer cells; these techniques, however, are usually not applied in the daily routine. Here, we present an ultra-high density (UHD SNParray technique which is, because of its high specificity and sensitivity and the combined copy number and allele information, highly appropriate for the genomic diagnosis of neuroblastoma and other malignancies.

  3. PPAR Gamma in Neuroblastoma: The Translational Perspectives of Hypoglycemic Drugs

    OpenAIRE

    Vella, Serena; Conaldi, Pier Giulio; Florio, Tullio; Pagano, Aldo

    2016-01-01

    Neuroblastoma (NB) is the most common and aggressive pediatric cancer, characterized by a remarkable phenotypic diversity and high malignancy. The heterogeneous clinical behavior, ranging from spontaneous remission to fatal metastatic disease, is attributable to NB biology and genetics. Despite major advances in therapies, NB is still associated with a high morbidity and mortality. Thus, novel diagnostic, prognostic, and therapeutic approaches are required, mainly to improve treatment outcome...

  4. Targeting neuroblastoma stem cells with retinoic acid and proteasome inhibitor.

    Directory of Open Access Journals (Sweden)

    Barbara Hämmerle

    Full Text Available Neuroblastma cell lines contain a side-population of cells which express stemness markers. These stem-like cells may represent the potential underlying mechanism for resistance to conventional therapy and recurrence of neuroblastoma in patients.To develop novel strategies for targeting the side-population of neurobastomas, we analyzed the effects of 13-cis-retinoic acid (RA combined with the proteasome inhibitor MG132. The short-term action of the treatment was compared with effects after a 5-day recovery period during which both chemicals were withdrawn. RA induced growth arrest and differentiation of SH-SY5Y and SK-N-BE(2 neuroblastoma cell lines. Inhibition of the proteasome caused apoptosis in both cell lines, thus, revealing the critical role of this pathway in the regulated degradation of proteins involved in neuroblastoma proliferation and survival. The combination of RA with MG132 induced apoptosis in a dose-dependent manner, in addition to promoting G2/M arrest in treated cultures. Interestingly, expression of stem cell markers such as Nestin, Sox2, and Oct4 were reduced after the recovery period of combined treatment as compared with untreated cells or treated cells with either compound alone. Consistent with this, neurosphere formation was significantly impaired by the combined treatment of RA and MG132.Given that stem-like cells are associated with resistant to conventional therapy and are thought to be responsible for relapse, our results suggest that dual therapy of RA and proteasome inhibitor might be beneficial for targeting the side-population of cells associated residual disease in high-risk neuroblastoma.

  5. Enhancement MRI evaluation of neuroblastoma staging in children

    International Nuclear Information System (INIS)

    Li Xin; Wang Chunxiang; Zhao Bin; Liu Peifang

    2002-01-01

    Objective: To evaluate the value and limitation of Gd-DTPA enhanced MRI for neuroblastoma staging in children. Methods: Twelve cases of neuroblastoma proved by operation or bone marrow aspiration were examined by gadolinium-enhanced MRI. The age ranged from seven months to five years, mean 3.7 years. Eight tumors originated from adrenal, and four from posterior mediastinum. Conventional sequences, double dose gadolinium-enhanced MRI, and 3D CEMRA were used in all patients. Six cases were examined by CT in same time. Imaging staging on surgic-histopathological-based International Neuroblastoma Staging System (INSS) was performed. Results: Six patients were staged by CT, including stage I-II in 2 cases, stage III in 4 cases, and stage IV in none. Twelve patients were staged by conventional MRI, including stage I-II in 2 cases, stage III in 9 cases, and stage IV in 1 case. Twelve patients were staged by double dose gadolinium-enhanced MRI, including stage I-II in 1 case, stage III in 1 case, and stage IV in 10 cases. Conclusion: Gadolinium-enhanced MRI was a single best imaging modality for neuroblastoma, most useful for distal to diaphragm metastasis, dumbbell tumor intraspinal extension, and bone marrow metastasis that was not detected by aspirate examination. Enhancement MRI was important in evaluating the therapy and was also helpful in assessing the therapeutic efficacy and relapse. 3D CEMRA helps demonstrate large vascular encasement and tumor erosion into important organs, and it is useful in assessing the respectability. Long examination time and lack in showing the characteristic calcium were the limitations

  6. Rapidly Evoluting Congenital Cystic Neuroblastoma in a Neonate

    Energy Technology Data Exchange (ETDEWEB)

    Yun, Tae Jun; Kim, Myung Jun; Han, Seok Joo; Lee, Mi Jung [Severance Children' s Hospital, Yonsei University, College of Medicine, Seoul(Korea, Republic of)

    2012-08-15

    Perinatal detection of neonatal suprarenal masses has increased. Here, we report an unusual case of an adrenal cystic neuroblastoma that presented as a purely cystic lesion upon initial postnatal ultrasonography (US) and showed rapid evolution to a mixed cystic and solid mass during follow-up US and MRI. We suggest a short-term (two weeks) follow-up US for neonatal adrenal cystic lesions, even if they appear as purely cystic.

  7. Protein kinase Cepsilon is important for migration of neuroblastoma cells

    International Nuclear Information System (INIS)

    Stensman, Helena; Larsson, Christer

    2008-01-01

    Migration is important for the metastatic capacity and thus for the malignancy of cancer cells. There is limited knowledge on regulatory factors that promote the migration of neuroblastoma cells. This study investigates the hypothesis that protein kinase C (PKC) isoforms regulate neuroblastoma cell motility. PKC isoforms were downregulated with siRNA or modulated with activators and inhibitors. Migration was analyzed with scratch and transwell assays. Protein phosphorylation and expression levels were measured with Western blot. Stimulation with 12-O-tetradecanoylphorbol-13-acetate (TPA) induced migration of SK-N-BE(2)C neuroblastoma cells. Treatment with the general protein kinase C (PKC) inhibitor GF109203X and the inhibitor of classical isoforms Gö6976 inhibited migration while an inhibitor of PKCβ isoforms did not have an effect. Downregulation of PKCε, but not of PKCα or PKCδ, with siRNA led to a suppression of both basal and TPA-stimulated migration. Experiments using PD98059 and LY294002, inhibitors of the Erk and phosphatidylinositol 3-kinase (PI3K) pathways, respectively, showed that PI3K is not necessary for TPA-induced migration. The Erk pathway might be involved in TPA-induced migration but not in migration driven by PKCε. TPA induced phosphorylation of the PKC substrate myristoylated alanine-rich C kinase substrate (MARCKS) which was suppressed by the PKC inhibitors. Treatment with siRNA oligonucleotides against different PKC isoforms before stimulation with TPA did not influence the phosphorylation of MARCKS. PKCε is important for migration of SK-N-BE(2)C neuroblastoma cells. Neither the Erk pathway nor MARCKS are critical downstream targets of PKCε but they may be involved in TPA-mediated migration

  8. Feasibility of magnetic marker localisation for non-palpable breast cancer.

    Science.gov (United States)

    Schermers, B; van der Hage, J A; Loo, C E; Vrancken Peeters, M T F D; Winter-Warnars, H A O; van Duijnhoven, F; Ten Haken, B; Muller, S H; Ruers, T J M

    2017-06-01

    Accurate tumour localisation is essential for breast-conserving surgery of non-palpable tumours. Current localisation technologies are associated with disadvantages such as logistical challenges and migration issues (wire guided localisation) or legislative complexities and high administrative burden (radioactive localisation). We present MAgnetic MArker LOCalisation (MaMaLoc), a novel technology that aims to overcome these disadvantages using a magnetic marker and a magnetic detection probe. This feasibility study reports on the first experience with this new technology for breast cancer localisation. Fifteen patients with unifocal, non-palpable breast cancer were recruited. They received concurrent placement of the magnetic marker in addition to a radioactive iodine seed, which is standard of care in our clinic. In a subset of five patients, migration of the magnetic marker was studied. During surgery, a magnetic probe and gammaprobe were alternately used to localise the markers and guide surgery. The primary outcome parameter was successful transcutaneous identification of the magnetic marker. Additionally, data on radiologist and surgeon satisfaction were collected. Magnetic marker placement was successful in all cases. Radiologists could easily adapt to the technology in the clinical workflow. Migration of the magnetic marker was negligible. The primary endpoint of the study was met with an identification rate of 100%. Both radiologists and surgeons reflected that the technology was intuitive to use and that it was comparable to radioactive iodine seed localisation. Magnetic marker localisation for non-palpable breast cancer is feasible and safe, and may be a viable non-radioactive alternative to current localisation technologies. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Disseminated peripheral neuroblastoma in a Rhodesian Ridgeback dog.

    Science.gov (United States)

    Cook, R W; Abraham, L A; McCowan, C I

    2017-04-01

    A 4-year-old neutered male Rhodesian Ridgeback dog with right-sided Horner's syndrome, bilateral laryngeal paralysis, neck pain and bilateral hindlimb ataxia was euthanased following deterioration of its neurological status. Necropsy examination revealed an off-white retropharyngeal neoplastic mass (100 × 30 × 30 mm) attached to the base of the skull on the right side and macroscopic nodular metastases in the spleen and three vertebral bodies (C6, C7 and T6), including a nodule attached to the dura at C7. Histological evidence of neuroblastic tumour was detected in these macroscopic lesions, a regional lymph node, bone marrow of a femur and all 15 vertebral bodies (C1-T8) examined, including the three with macroscopic metastases, and in the lumens of small blood vessels in the lungs and liver. Ganglion cell differentiation was detected only in the primary retropharyngeal mass, one splenic nodule and the C7 dural nodule. Neoplastic cells were immunoreactive to neurofilament protein (ganglion cells only), vimentin and synaptophysin, and were negative for S100 protein, GFAP, CD3 and Pax5. The diagnosis was disseminated peripheral neuroblastoma, differentiating subtype (International Neuroblastoma Pathology Classification), with likely primary involvement of the right cranial cervical ganglion. This appears to be the first report of neuroblastoma in a dog with widespread occult haematogenous metastasis to bone marrow. © 2017 Australian Veterinary Association.

  10. The genetic landscape of high-risk neuroblastoma.

    Science.gov (United States)

    Pugh, Trevor J; Morozova, Olena; Attiyeh, Edward F; Asgharzadeh, Shahab; Wei, Jun S; Auclair, Daniel; Carter, Scott L; Cibulskis, Kristian; Hanna, Megan; Kiezun, Adam; Kim, Jaegil; Lawrence, Michael S; Lichenstein, Lee; McKenna, Aaron; Pedamallu, Chandra Sekhar; Ramos, Alex H; Shefler, Erica; Sivachenko, Andrey; Sougnez, Carrie; Stewart, Chip; Ally, Adrian; Birol, Inanc; Chiu, Readman; Corbett, Richard D; Hirst, Martin; Jackman, Shaun D; Kamoh, Baljit; Khodabakshi, Alireza Hadj; Krzywinski, Martin; Lo, Allan; Moore, Richard A; Mungall, Karen L; Qian, Jenny; Tam, Angela; Thiessen, Nina; Zhao, Yongjun; Cole, Kristina A; Diamond, Maura; Diskin, Sharon J; Mosse, Yael P; Wood, Andrew C; Ji, Lingyun; Sposto, Richard; Badgett, Thomas; London, Wendy B; Moyer, Yvonne; Gastier-Foster, Julie M; Smith, Malcolm A; Guidry Auvil, Jaime M; Gerhard, Daniela S; Hogarty, Michael D; Jones, Steven J M; Lander, Eric S; Gabriel, Stacey B; Getz, Gad; Seeger, Robert C; Khan, Javed; Marra, Marco A; Meyerson, Matthew; Maris, John M

    2013-03-01

    Neuroblastoma is a malignancy of the developing sympathetic nervous system that often presents with widespread metastatic disease, resulting in survival rates of less than 50%. To determine the spectrum of somatic mutation in high-risk neuroblastoma, we studied 240 affected individuals (cases) using a combination of whole-exome, genome and transcriptome sequencing as part of the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) initiative. Here we report a low median exonic mutation frequency of 0.60 per Mb (0.48 nonsilent) and notably few recurrently mutated genes in these tumors. Genes with significant somatic mutation frequencies included ALK (9.2% of cases), PTPN11 (2.9%), ATRX (2.5%, and an additional 7.1% had focal deletions), MYCN (1.7%, causing a recurrent p.Pro44Leu alteration) and NRAS (0.83%). Rare, potentially pathogenic germline variants were significantly enriched in ALK, CHEK2, PINK1 and BARD1. The relative paucity of recurrent somatic mutations in neuroblastoma challenges current therapeutic strategies that rely on frequently altered oncogenic drivers.

  11. The genetic landscape of high-risk neuroblastoma

    Science.gov (United States)

    Pugh, Trevor J.; Morozova, Olena; Attiyeh, Edward F.; Asgharzadeh, Shahab; Wei, Jun S.; Auclair, Daniel; Carter, Scott L.; Cibulskis, Kristian; Hanna, Megan; Kiezun, Adam; Kim, Jaegil; Lawrence, Michael S.; Lichenstein, Lee; McKenna, Aaron; Pedamallu, Chandra Sekhar; Ramos, Alex H.; Shefler, Erica; Sivachenko, Andrey; Sougnez, Carrie; Stewart, Chip; Ally, Adrian; Birol, Inanc; Chiu, Readman; Corbett, Richard D.; Hirst, Martin; Jackman, Shaun D.; Kamoh, Baljit; Khodabakshi, Alireza Hadj; Krzywinski, Martin; Lo, Allan; Moore, Richard A.; Mungall, Karen L.; Qian, Jenny; Tam, Angela; Thiessen, Nina; Zhao, Yongjun; Cole, Kristina A.; Diamond, Maura; Diskin, Sharon J.; Mosse, Yael P.; Wood, Andrew C.; Ji, Lingyun; Sposto, Richard; Badgett, Thomas; London, Wendy B.; Moyer, Yvonne; Gastier-Foster, Julie M.; Smith, Malcolm A.; Auvil, Jaime M. Guidry; Gerhard, Daniela S.; Hogarty, Michael D.; Jones, Steven J. M.; Lander, Eric S.; Gabriel, Stacey B.; Getz, Gad; Seeger, Robert C.; Khan, Javed; Marra, Marco A.; Meyerson, Matthew; Maris, John M.

    2013-01-01

    Neuroblastoma is a malignancy of the developing sympathetic nervous system that often presents with widespread metastatic disease, resulting in survival rates of less than 50%1. To determine the spectrum of somatic mutation in high-risk neuroblastoma, we studied 240 cases using a combination of whole exome, genome and transcriptome sequencing as part of the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) initiative. Here we report a low median exonic mutation frequency of 0.60 per megabase (0.48 non-silent), and remarkably few recurrently mutated genes in these tumors. Genes with significant somatic mutation frequencies included ALK (9.2% of cases), PTPN11 (2.9%), ATRX (2.5%, an additional 7.1% had focal deletions), MYCN (1.7%, a recurrent p.Pro44Leu alteration), and NRAS (0.83%). Rare, potentially pathogenic germline variants were significantly enriched in ALK, CHEK2, PINK1, and BARD1. The relative paucity of recurrent somatic mutations in neuroblastoma challenges current therapeutic strategies reliant upon frequently altered oncogenic drivers. PMID:23334666

  12. Intrarenal neuroblastoma - a diagnostic dilemma: A report of three cases

    Directory of Open Access Journals (Sweden)

    Anupam Lall

    2001-01-01

    Full Text Available Differentiation between the Wilms′ tumor (WT and the intrarenal neuroblastoma (IRNB is imperative, as the prognosis and the treatment are different for these condi-tions. It may pose a diagnostic challenge to distinguish them pre-operatively. Over the period of last 10 years (1990-1999, 3 children aged 2 months to 4 years were diagnosed to have IRNB. 2 cases were operated with a provisional diagnosis of WT, but on histology were found to have neuroblastoma. Taking benefit from our previous experience, the third case we encountered with a renal lump and bony metastasis with clinical features not con-sistent with the diagnosis of Wilms′ tumor was further investigated. Urinary catecholamines were significantly elevated and there was bone marrow involvement and positive bone scan for multiple bony metastasis. 2 pa-tients are on chemotherapy and follow-up for last 6 months, while 1 died 6 years back after a follow-up of 2 years. Patients who have a renal mass on imaging, with clinical features of rapid deterioration in general condi-tion and evidence of bony secondaries, should undergo work-up for neuroblastoma pre-operatively to confirm the diagnosis.

  13. Nuclear medicine and multimodality imaging of pediatric neuroblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Mueller, Wolfgang Peter; Pfluger, Thomas [Ludwig-Maximilians-University of Munich, Department of Nuclear Medicine, Munich (Germany); Coppenrath, Eva [Ludwig-Maximilians-University of Munich, Department of Radiology, Munich (Germany)

    2013-04-15

    Neuroblastoma is an embryonic tumor of the peripheral sympathetic nervous system and is metastatic or high risk for relapse in nearly 50% of cases. Therefore, exact staging with radiological and nuclear medicine imaging methods is crucial for defining the adequate therapeutic choice. Tumor cells express the norepinephrine transporter, which makes metaiodobenzylguanidine (MIBG), an analogue of norepinephrine, an ideal tumor specific agent for imaging. MIBG imaging has several disadvantages, such as limited spatial resolution, limited sensitivity in small lesions and the need for two or even more acquisition sessions. Most of these limitations can be overcome with positron emission tomography (PET) using [F-18]2-fluoro-2-deoxyglucose [FDG]. Furthermore, new tracers, such as fluorodopa or somatostatin receptor agonists, have been tested for imaging neuroblastoma recently. However, MIBG scintigraphy and PET alone are not sufficient for operative or biopsy planning. In this regard, a combination with morphological imaging is indispensable. This article will discuss strategies for primary and follow-up diagnosis in neuroblastoma using different nuclear medicine and radiological imaging methods as well as multimodality imaging. (orig.)

  14. Malformation/dysplasia syndrome (neural tube defect, hypospadias neuroblastoma) associated with an extra dicentric marker chromosome 15 ({open_quotes}inversion duplication 15{close_quotes})

    Energy Technology Data Exchange (ETDEWEB)

    Reitnauer, P.J.; Rao, K.W.; Tepperberg, J.H. [Univ. of North Carolina, Chapel Hill, NC (United States)

    1994-09-01

    Extra dicentric 15 marker chromosomes are associated with variable degrees of mental retardation but not major structural birth defects. We have studied a unique patient, a male infant who was prenatally diagnosed with lumbar meningomyelocele and an extra pseudodicentric marker chromosome: 47,XY,+psu dic(15)t(15;15)(?q12,?q12)mat. Hairy ears and a coronal hypospadias were noted at birth. At three months of age, a stage I thoracic neuroblastoma was primarily resected. Tumor cells, skin fibroblasts and peripheral blood lymphocytes contained the dicentric 15. The mother is mosaic for the marker chromosome. Fluorescence in situ hybridization (FISH) studies using a classic 15 satellite probe (D15Z1 [Oncor]) confirmed the presence of 2 number 15 centromeres in the marker. The marker is felt to be the result of a translocation rather than an inverted duplication because the G-band morphology of the short arm/satellite complexes differ from one another, implying that the arms originate from 2 different number 15s. FISH analysis using cosmid probes for the Prader-Willi/Angelman critical region (D15S11 and GABRB3 [Oncor]) revealed 2 copies of this region, indicating that these loci are duplicated in the marker. Although some features of the patient`s phenotype such as developmental delay and hypotonia have been associated with dicentric chromosome 15 markers, this is the first malformation/dysplasia syndrome or neuroblastoma reported to our knowledge. The association of neuroblastoma with chromosome 15 aberrations in this case provides speculation as to the role of chromosome 15 loci in cell division control.

  15. [Pelvic reconstructions after bone tumor resection].

    Science.gov (United States)

    Anract, Philippe; Biau, David; Babinet, Antoine; Tomeno, Bernard

    2014-02-01

    The three more frequent primitive malignant bone tumour which concerned the iliac bone are chondrosarcoma, following Ewing sarcoma and osteosarcoma. Wide resection remains the most important part of the treatment associated with chemotherapy for osteosarcoma and the Ewing sarcoma. Iliac wing resections and obdurate ring don't required reconstruction. However, acetabular resections and iliac wing resection with disruption of the pelvic ring required reconstruction to provide acceptable functional result. Acetabular reconstruction remains high technical demanding challenge. After isolated acetabular resection or associated to obdurate ring, our usual method of reconstruction is homolateral proximal femoral autograft and total hip prosthesis but it is possible to also used : saddle prosthesis, Mac Minn prosthesis with auto or allograft, modular prosthesis or custom made prosthesis, massive allograft with or without prosthesis and femoro-ilac arthrodesis. After resection of the iliac wing plus acetabulum, reconstruction can be performed by femoro-obturatrice and femora-sacral arthrodesis, homolateral proximal femoral autograft and prosthesis, femoral medialisation, massive allograft and massive allograft. Carcinological results are lesser than resection for distal limb tumor, local recurrence rate range 17 to 45%. Functional results after Iliac wing and obdurate ring are good. However, acetabular reconstruction provide uncertain functional results. The lesser results arrive after hemipelvic or acetabular and iliac wing resection-reconstruction, especially when gluteus muscles were also resected. The most favourable results arrive after isolated acetabular or acetabular plus obturateur ring resection-reconstruction.

  16. Prospective evaluation of the International Neuroblastoma Staging System (INSS) and the International Neuroblastoma Response Criteria (INRC) in a multicentre setting.

    Science.gov (United States)

    Castel, V; García-Miguel, P; Cañete, A; Melero, C; Navajas, A; Ruíz-Jiménez, J I; Navarro, S; Badal, M D

    1999-04-01

    The aim of this study was to classify prospectively a series of neuroblastoma tumours according to the International Neuroblastoma Staging System (INSS) and the International Neuroblastoma Response Criteria (INRC) and to evaluate the difficulties and pitfalls involved in a multicentre setting. Each hospital provided their data for central review. The surgical procedures and their complications were reported. Kaplan-Meier estimates of survival and event-free survival were calculated according to stage and response to therapy. From June 1992 to December 1996, 194 patients were included in the study, with a mean age of 2 years. Initial studies were performed according to INSS recommendations without major problems. INSS stage was correctly applied to all patients except for 9 (95%). Post-operative complications were observed in 15 patients (8.3%). Response to therapy (INRC) was studied in 63 stage 4 patients, 11 of whom were not classified correctly (17%). Differences in survival according to stage (INSS) and group of response to therapy (INRC) were statistically significant (P INSS was easy to use and separated different prognostic groups. Surgical complications and mortality did not increase in this series because of using the INSS. The feasibility of INRC was evaluated in a small series of stage 4 patients and the designation of response was problematic in a relatively high proportion of cases. The prognostic value of the different responses was highly significant, but less informative than had been hoped for.

  17. Allelic loss of chromosome 1p as a predictor of unfavorable outcome in patients with neuroblastoma

    NARCIS (Netherlands)

    H.N. Caron (Huib); P. van Sluis (Peter); J. de Kraker (Jan); J.P. Bökkerink (Jos); R.M. Egeler (Maarten); G. Laureys (Geneviève); R. Slater (Rosalyn); A. Westerveld (Andries); M.T. Voûte (Michiel); R. Versteeg (Rogier)

    1996-01-01

    textabstractBackground. Neuroblastoma is a childhood tumor derived from cells of the neural crest, with a widely variable outcome. Differences in the behavior and prognosis of the tumor suggest that neuroblastoma can be divided into several biologic subgroups. We evaluated the most frequent genetic

  18. Allelic loss of chromosome 1p as a predictor of unfavorable outcome in patients with neuroblastoma

    NARCIS (Netherlands)

    Caron, H.; van Sluis, P.; de Kraker, J.; Bökkerink, J.; Egeler, M.; Laureys, G.; Slater, R.; Westerveld, A.; Voûte, P. A.; Versteeg, R.

    1996-01-01

    Neuroblastoma is a childhood tumor derived from cells of the neural crest, with a widely variable outcome. Differences in the behavior and prognosis of the tumor suggest that neuroblastoma can be divided into several biologic subgroups. We evaluated the most frequent genetic abnormalities in

  19. Ataxia-telangiectasia mutated (ATM) silencing promotes neuroblastoma progression through a MYCN independent mechanism

    Science.gov (United States)

    Mandriota, Stefano J.; Valentijn, Linda J.; Lesne, Laurence; Betts, David R.; Marino, Denis; Boudal-Khoshbeen, Mary; London, Wendy B.; Rougemont, Anne-Laure; Attiyeh, Edward F.; Maris, John M.; Hogarty, Michael D.; Koster, Jan; Molenaar, Jan J.; Versteeg, Rogier

    2015-01-01

    Neuroblastoma, a childhood cancer with highly heterogeneous biology and clinical behavior, is characterized by genomic aberrations including amplification of MYCN. Hemizygous deletion of chromosome 11q is a well-established, independent marker of poor prognosis. While 11q22-q23 is the most frequently deleted region, the neuroblastoma tumor suppressor in this region remains to be identified. Chromosome bands 11q22-q23 contain ATM, a cell cycle checkpoint kinase and tumor suppressor playing a pivotal role in the DNA damage response. Here, we report that haploinsufficiency of ATM in neuroblastoma correlates with lower ATM expression, event-free survival, and overall survival. ATM loss occurs in high stage neuroblastoma without MYCN amplification. In SK-N-SH, CLB-Ga and GI-ME-N human neuroblastoma cells, stable ATM silencing promotes neuroblastoma progression in soft agar assays, and in subcutaneous xenografts in nude mice. This effect is dependent on the extent of ATM silencing and does not appear to involve MYCN. Our findings identify ATM as a potential haploinsufficient neuroblastoma tumor suppressor, whose inactivation mirrors the increased aggressiveness associated with 11q deletion in neuroblastoma. PMID:26053094

  20. Heparin-binding epidermal growth factor-like growth factor promotes neuroblastoma differentiation.

    Science.gov (United States)

    Gaviglio, Angela L; Knelson, Erik H; Blobe, Gerard C

    2017-05-01

    High-risk neuroblastoma is characterized by undifferentiated neuroblasts and low schwannian stroma content. The tumor stroma contributes to the suppression of tumor growth by releasing soluble factors that promote neuroblast differentiation. Here we identify heparin-binding epidermal growth factor-like growth factor (HBEGF) as a potent prodifferentiating factor in neuroblastoma. HBEGF mRNA expression is decreased in human neuroblastoma tumors compared with benign tumors, with loss correlating with decreased survival. HBEGF protein is expressed only in stromal compartments of human neuroblastoma specimens, with tissue from high-stage disease containing very little stroma or HBEGF expression. In 3 human neuroblastoma cell lines (SK-N-AS, SK-N-BE2, and SH-SY5Y), soluble HBEGF is sufficient to promote neuroblast differentiation and decrease proliferation. Heparan sulfate proteoglycans and heparin derivatives further enhance HBEGF-induced differentiation by forming a complex with the epidermal growth factor receptor, leading to activation of the ERK1/2 and STAT3 pathways and up-regulation of the inhibitor of DNA binding transcription factor. These data support a role for loss of HBEGF in the neuroblastoma tumor microenvironment in neuroblastoma pathogenesis.-Gaviglio, A. L., Knelson, E. H., Blobe, G. C. Heparin-binding epidermal growth factor-like growth factor promotes neuroblastoma differentiation. © FASEB.

  1. Convolutional deep belief network with feature encoding for classification of neuroblastoma histological images

    Directory of Open Access Journals (Sweden)

    Soheila Gheisari

    2018-01-01

    Full Text Available Background: Neuroblastoma is the most common extracranial solid tumor in children younger than 5 years old. Optimal management of neuroblastic tumors depends on many factors including histopathological classification. The gold standard for classification of neuroblastoma histological images is visual microscopic assessment. In this study, we propose and evaluate a deep learning approach to classify high-resolution digital images of neuroblastoma histology into five different classes determined by the Shimada classification. Subjects and Methods: We apply a combination of convolutional deep belief network (CDBN with feature encoding algorithm that automatically classifies digital images of neuroblastoma histology into five different classes. We design a three-layer CDBN to extract high-level features from neuroblastoma histological images and combine with a feature encoding model to extract features that are highly discriminative in the classification task. The extracted features are classified into five different classes using a support vector machine classifier. Data: We constructed a dataset of 1043 neuroblastoma histological images derived from Aperio scanner from 125 patients representing different classes of neuroblastoma tumors. Results: The weighted average F-measure of 86.01% was obtained from the selected high-level features, outperforming state-of-the-art methods. Conclusion: The proposed computer-aided classification system, which uses the combination of deep architecture and feature encoding to learn high-level features, is highly effective in the classification of neuroblastoma histological images.

  2. Natural killer cells facilitate PRAME-specific T-cell reactivity against neuroblastoma

    NARCIS (Netherlands)

    Spel, Lotte; Boelens, Jaap Jan; Van Der Steen, Dirk M.; Blokland, Nina J G; van Noesel, Max M.; Molenaar, Jan J.; Heemskerk, Mirjam H M; Boes, Marianne; Nierkens, Stefan

    2015-01-01

    Neuroblastoma is the most common solid tumor in children with an estimated 5-year progression free survival of 20-40% in stage 4 disease. Neuroblastoma actively avoids recognition by natural killer (NK) cells and cytotoxic T lymphocytes (CTLs). Although immunotherapy has gained traction for

  3. The association between neuroblastoma and opsoclonus-myoclonus syndrome: a historical review

    International Nuclear Information System (INIS)

    Rothenberg, Alexis B.; Berdon, Walter E.; D'Angio, Giulio J.; Yamashiro, Darrell J.; Cowles, Robert A.

    2009-01-01

    An association between neuroblastoma and opsoclonus-myoclonus syndrome (OMS) was described as early as 1927 within the first report on the transformation of malignant neuroblastoma to a benign ganglioneuroma. It was not recognized at that time nor was it appreciated in the subsequent follow-up report on the same patient in 1959. Myoclonic encephalopathy of infancy, an alternative name for OMS, was described by a pediatric neurologist in 1962; however, its connection to neuroblastoma was not known. It was only in 1968 that the association between these two conditions was first reported. The neuroblastoma tumors associated with OMS are almost all small, stage I-II with no associated MYCN amplification or metastases. OMS occurs in 2-3% of patients with neuroblastoma, but neuroblastoma is found in as many as 50% of children who present with OMS. Nearly 100% of the children with neuroblastoma associated with OMS survive, and this has led to speculation that the OMS is a result of an autoimmune process, not metastases. Affected children are treated with steroids, ACTH, or intravenous immunoglobulin, but many have persistent neurologic and developmental deficits. Using the original case reported in 1927, we summarize a century of literature in this review on OMS and its association with neuroblastoma. (orig.)

  4. Synergistic interaction between cisplatin and gemcitabine in neuroblastoma cell lines and multicellular tumor spheroids

    NARCIS (Netherlands)

    Besançon, Odette G.; Tytgat, Godelieve A. M.; Meinsma, Rutger; Leen, René; Hoebink, Jerry; Kalayda, Ganna V.; Jaehde, Ulrich; Caron, Huib N.; van Kuilenburg, André B. P.

    2012-01-01

    The efficacy and mechanism of action of cisplatin and gemcitabine were investigated in a panel of neuroblastoma cell lines and multicellular tumor spheroids. In neuroblastoma spheroids, the combination of cisplatin and gemcitabine induced a complete cytostasis at clinical relevant concentrations. A

  5. Meta-analysis of Neuroblastomas Reveals a Skewed ALK Mutation Spectrum in Tumors with MYCN Amplification

    NARCIS (Netherlands)

    de Brouwer, Sara; de Preter, Katleen; Kumps, Candy; Zabrocki, Piotr; Porcu, Michaël; Westerhout, Ellen M.; Lakeman, Arjan; Vandesompele, Jo; Hoebeeck, Jasmien; van Maerken, Tom; de Paepe, Anne; Laureys, Geneviève; Schulte, Johannes H.; Schramm, Alexander; van den Broecke, Caroline; Vermeulen, Joëlle; van Roy, Nadine; Beiske, Klaus; Renard, Marleen; Noguera, Rosa; Delattre, Olivier; Janoueix-Lerosey, Isabelle; Kogner, Per; Martinsson, Tommy; Nakagawara, Akira; Ohira, Miki; Caron, Huib N.; Eggert, Angelika; Cools, Jan; Versteeg, Rogier; Speleman, Frank

    2010-01-01

    Purpose: Activating mutations of the anaplastic lymphoma kinase (ALK) were recently described in neuroblastoma. We carried out a meta-analysis of 709 neuroblastoma tumors to determine their frequency and mutation spectrum in relation to genomic and clinical parameters, and studied the prognostic

  6. Can Image-Defined Risk Factors Predict Surgical Complications in Localized Neuroblastoma?

    Science.gov (United States)

    Yoneda, Akihiro; Nishikawa, Masanori; Uehara, Shuichiro; Oue, Takaharu; Usui, Noriaki; Inoue, Masami; Fukuzawa, Masahiro; Okuyama, Hiroomi

    2016-02-01

    Image-defined risk factors (IDRFs) have been propounded for predicting the surgical risks associated with localized neuroblastoma (NB) since 2009. In 2011, a new guideline (NG) for assessing IDRFs was published. According to the NG, the situation in which "the tumor is only in contact with renal vessels," should be considered to be "IDRF-present." Previously, this situation was diagnosed as "IDRF absent." In this study, we evaluated the IDRFs in localized NB patients to clarify the predictive capability of IDRFs for surgical complications, as well as the usefulness of the NG. Materials and A total of 107 localized patients with NB were included in this study. The enhanced computed tomography and magnetic resonance images from the time of their diagnoses were evaluated by a single radiologist. We also analyzed the association of clinical factors, including the IDRFs (before and after applying the NG), with surgical complications. Of the 107 patients, 33 and 74 patients were diagnosed as IDRF-present (OP group), and IDRF-absent (ON group) before the NG, respectively. According to the NG, there were 76 and 31 patients who were classified as IDRF-present (NP group) and IDRF absent (NN group), respectively. Thus, 43 (40%) patients in the ON group were reassigned to the NP group after the NG. Surgical complications were observed in 17 of 82 patients who underwent surgical resection. Of the patients who underwent secondary operations, surgical complication rates were 55% in the OP group and 44% in the NP group. According to a univariate analysis, non-INSS 1, IDRFs before and after the NG and secondary operations were significantly associated with surgical complications. In a multivariate analysis, non-INSS 1 status and IDRFs after the NG were significantly associated with surgical complications. Georg Thieme Verlag KG Stuttgart · New York.

  7. Localised boundary air layer and clothing evaporative resistances for individual body segments.

    Science.gov (United States)

    Wang, Faming; del Ferraro, Simona; Lin, Li-Yen; Sotto Mayor, Tiago; Molinaro, Vincenzo; Ribeiro, Miguel; Gao, Chuansi; Kuklane, Kalev; Holmér, Ingvar

    2012-01-01

    Evaporative resistance is an important parameter to characterise clothing thermal comfort. However, previous work has focused mainly on either total static or dynamic evaporative resistance. There is a lack of investigation of localised clothing evaporative resistance. The objective of this study was to study localised evaporative resistance using sweating thermal manikins. The individual and interaction effects of air and body movements on localised resultant evaporative resistance were examined in a strict protocol. The boundary air layer's localised evaporative resistance was investigated on nude sweating manikins at three different air velocity levels (0.18, 0.48 and 0.78 m/s) and three different walking speeds (0, 0.96 and 1.17 m/s). Similarly, localised clothing evaporative resistance was measured on sweating manikins at three different air velocities (0.13, 0.48 and 0.70 m/s) and three walking speeds (0, 0.96 and 1.17 m/s). Results showed that the wind speed has distinct effects on local body segments. In contrast, walking speed brought much more effect on the limbs, such as thigh and forearm, than on body torso, such as back and waist. In addition, the combined effect of body and air movement on localised evaporative resistance demonstrated that the walking effect has more influence on the extremities than on the torso. Therefore, localised evaporative resistance values should be provided when reporting test results in order to clearly describe clothing local moisture transfer characteristics. Localised boundary air layer and clothing evaporative resistances are essential data for clothing design and assessment of thermal comfort. A comprehensive understanding of the effects of air and body movement on localised evaporative resistance is also necessary by both textile and apparel researchers and industry.

  8. Optimal localisation of next generation Biofuel production in Sweden

    Energy Technology Data Exchange (ETDEWEB)

    Wetterlund, Elisabeth [Linkoeping Univ., Linkoeping (Sweden); Pettersson, Karin [Chalmers Univ. of Technology, Goeteborg (Sweden); Mossberg, Johanna [SP Technical Research Inst. of Sweden, Boraas (Sweden)] [and others

    2013-09-01

    With a high availability of lignocellulosic biomass and various types of cellulosic by-products, as well as a large number of industries, Sweden is a country of great interest for future large scale production of sustainable, next generation biofuels. This is most likely also a necessity as Sweden has the ambition to be independent of fossil fuels in the transport sector by the year 2030 and completely fossil free by 2050. In order to reach competitive biofuel production costs, plants with large production capacities are likely to be required. Feedstock intake capacities in the range of about 1-2 million tonnes per year, corresponding to a biomass feed of 300-600 MW, can be expected, which may lead to major logistical challenges. To enable expansion of biofuel production in such large plants, as well as provide for associated distribution requirements, it is clear that substantial infrastructure planning will be needed. The geographical location of the production plant facilities is therefore of crucial importance and must be strategic to minimise the transports of raw material as well as of final product. Competition for the available feedstock, from for example forest industries and CHP plants (combined heat and power) further complicates the localisation problem. Since the potential for an increased biomass utilisation is limited, high overall resource efficiency is of great importance. Integration of biofuel production processes in existing industries or in district heating systems may be beneficial from several aspects, such as opportunities for efficient heat integration, feedstock and equipment integration, as well as access to existing experience and know-how. This report describes the development of Be Where Sweden, a geographically explicit optimisation model for localisation of next generation biofuel production plants in Sweden. The main objective of developing such a model is to be able to assess production plant locations that are robust to varying

  9. The Role of Intracellular Calcium for the Development and Treatment of Neuroblastoma

    International Nuclear Information System (INIS)

    Satheesh, Noothan Jyothi; Büsselberg, Dietrich

    2015-01-01

    Neuroblastoma is the second most common paediatric cancer. It develops from undifferentiated simpatico-adrenal lineage cells and is mostly sporadic; however, the aetiology behind the development of neuroblastoma is still not fully understood. Intracellular calcium ([Ca 2+ ] i ) is a secondary messenger which regulates numerous cellular processes and, therefore, its concentration is tightly regulated. This review focuses on the role of [Ca 2+ ] i in differentiation, apoptosis and proliferation in neuroblastoma. It describes the mechanisms by which [Ca 2+ ] i is regulated and how it modulates intracellular pathways. Furthermore, the importance of [Ca 2+ ] i for the function of anti-cancer drugs is illuminated in this review as [Ca 2+ ] i could be a target to improve the outcome of anti-cancer treatment in neuroblastoma. Overall, modulations of [Ca 2+ ] i could be a key target to induce apoptosis in cancer cells leading to a more efficient and effective treatment of neuroblastoma

  10. Therapeutic Innovations for Targeting Childhood Neuroblastoma: Implications of the Neurokinin-1 Receptor System.

    Science.gov (United States)

    Berger, Michael; VON Schweinitz, Dietrich

    2017-11-01

    Neuroblastoma is the most common solid extracranial malignant tumor in children. Despite recent advances in the treatment of this heterogenous tumor with surgery and chemotherapy, the prognosis in advanced stages remains poor. Interestingly, neuroblastoma is one of the few solid tumors, to date, in which an effect for targeted immunotherapy has been proven in controlled clinical trials, giving hope for further advances in the treatment of this and other tumors by targeted therapy. A large array of novel therapeutic options for targeted therapy of neuroblastoma is on the horizon. To this repεrtoirε, the neurokinin-1 receptor (NK1R) system was recently added. The present article explores the most recent developments in targeting neuroblastoma cells via the NK1R and how this new knowledge could be helpful to create new anticancer therapies agains neuroblastoma and other cancers. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  11. Lapatinib potentiates cytotoxicity of YM155 in neuroblastoma via inhibition of the ABCB1 efflux transporter

    DEFF Research Database (Denmark)

    Radic-Sarikas, Branka; Halasz, Melinda; Huber, Kilian V. M.

    2017-01-01

    and simultaneously help to overcome drug resistance. Neuroblastoma is the most common cancer in infancy and extremely heterogeneous in clinical presentation and features. Applying a systematic pairwise drug combination screen we observed a highly potent synergy in neuroblastoma cells between the EGFR kinase...... inhibitor lapatinib and the anticancer compound YM155 that is preserved across several neuroblastoma variants. Mechanistically, the synergy was based on a lapatinib induced inhibition of the multidrug-resistance efflux transporter ABCB1, which is frequently expressed in resistant neuroblastoma cells, which...... allowed prolonged and elevated cytotoxicity of YM155. In addition, the drug combination (i.e. lapatinib plus YM155) decreased neuroblastoma tumor size in an in vivo model....

  12. Ectopic olfactory neuroblastoma: report of four cases and a review of the literature.

    LENUS (Irish Health Repository)

    Wormald, R

    2011-04-01

    Our objective is to present a short series of four rare cases of ectopic olfactory neuroblastoma. Our methods present four case reports of ectopic olfactory neuroblastoma and a review of the literature for management and treatment of this disease. The results indicate short case series reports of ectopic olfactory neuroblastoma arising from the anterior ethmoidal sinuses, the nasopharynx, the lateral nasal wall and the floor of the nose. The discussion focuses on likely origins of ectopic olfactory neuroblastoma, its clinical features and management. We conclude that ectopic olfactory neuroblastoma is a rare disease. Treatment principles are the same for non-ectopic disease and guided by extension into adjacent structures such as the orbit or anterior cranial fossa and usually involves surgery with or without adjuvant radiotherapy.

  13. Radioguided localisation of impalpable breast lesions using 99m-Technetium macroaggregated albumin: Lessons learnt during introduction of a new technique to guide preoperative localisation

    Energy Technology Data Exchange (ETDEWEB)

    Landman, Joanne [Department of Nuclear Medicine, Royal Perth Hospital, Perth, Western Australia (Australia); Kulawansa, Sagarika [Department of Diagnostic and Interventional Radiology, Royal Perth Hospital, Perth, Western Australia (Australia); McCarthy, Michael; Troedson, Russell [Department of Nuclear Medicine, Royal Perth Hospital, Perth, Western Australia (Australia); Phillips, Michael [Western Australian Institute for Medical Research, University of Western Australia, Perth, Western Australia (Australia); Tinning, Jill [The Multidisciplinary Breast Service, Royal Perth Hospital, Perth, Western Australia (Australia); Taylor, Donna, E-mail: Donna.Taylor@health.wa.gov.au [Department of Diagnostic and Interventional Radiology, Royal Perth Hospital, Perth, Western Australia (Australia); School of Surgery, University of Western Australia, Perth, Western Australia (Australia); Department of Nuclear Medicine, Royal Perth Hospital, Perth, Western Australia (Australia)

    2015-03-15

    Preoperative wire-guided localisation (WGL) of impalpable breast lesions is widely used but can be technically difficult. Risks include wire migration, inaccurate placement, and inadequate surgical margins. Research shows that radioguided occult lesion localisation (ROLL) is quicker, easier, and can improve surgical and cosmetic outcomes. An audited introduction of ROLL was conducted to validate the technique as a feasible alternative to WGL. Fifty patients with single impalpable lesions and biopsy proven malignancy or indeterminate histology underwent WGL followed by intralesional radiopharmaceutical injection of 99m-Technetium macroaggregated albumin. Postprocedural mammography was performed to demonstrate wire position, and scintigraphy to evaluate radiopharmaceutical migration. Lymphoscintigraphy and intraoperative sentinel node biopsy were performed if indicated, followed by lesion localisation and excision using a gamma probe. Specimen imaging was performed, with immediate reexcision for visibly inadequate margins. Accurate localisation was achieved in 86% of patients with ROLL compared to 72% with WGL. All lesions were successfully removed, with clear margins in 71.8% of malignant lesions. Reexcision and intraoperative sentinel node localisation rates were equivalent to preaudit figures for WGL. ROLL was easy to perform and problems were infrequent. Inaccurate radiopharmaceutical placement necessitating WGL occurred in four patients. Minor radiopharmaceutical migration was common, but precluded using ROLL in only two cases. ROLL is effective, simple, inexpensive, and easily learnt; however, preoperative confirmation of correct radiopharmaceutical placement using mammography and the gamma probe is important to help ensure successful lesion removal. Insertion of a backup hookwire is recommended during the initial introduction of ROLL.

  14. Managing Potentially Resectable Metastatic Colon Cancer

    OpenAIRE

    Marshall, John L.

    2008-01-01

    For patients with metastatic colon cancer, management has evolved from resecting a single liver metastasis and having only one chemotherapy medicine, to resecting multiple metastases including those outside the liver as well as using combination chemotherapy (based on recent supportive trials) to improve outcomes. This success has also raised many questions, including the role of adjuvant chemotherapy to downstage borderline resectable tumors, whether patients who receive preoperative chemoth...

  15. Robotic vascular resections during Whipple procedure.

    Science.gov (United States)

    Allan, Bassan J; Novak, Stephanie M; Hogg, Melissa E; Zeh, Herbert J

    2018-01-01

    Indications for resection of pancreatic cancers have evolved to include selected patients with involvement of peri-pancreatic vascular structures. Open Whipple procedures have been the standard approach for patients requiring reconstruction of the portal vein (PV) or superior mesenteric vein (SMV). Recently, high-volume centers are performing minimally invasive Whipple procedures with portovenous resections. Our institution has performed seventy robotic Whipple procedures with concomitant vascular resections. This report outlines our technique.

  16. Liver resection over the last decade

    DEFF Research Database (Denmark)

    Wettergren, A.; Larsen, P.N.; Rasmussen, A.

    2008-01-01

    after resection of hepatic metastases from colorectal cancer and hepatocellular carcinoma was estimated. RESULTS: 141 patients (71M/70F), median age 58 years (1-78), underwent a liver resection in the ten-year period. The number of resections increased from two in 1995 to 32 in 2004. Median hospital...... stay was 9 days (3-38). The most frequent complication was biliary leakage (7.8%), haemorrhage (2.8%) and hepatic insufficiency (2.8%). 30-days mortality was 1.4%. The actuarial 5-survival after hepatic resection for colorectal liver metastases and hepatocellular carcinoma was 39% and 42%, respectively...

  17. Liver resection over the last decade

    DEFF Research Database (Denmark)

    Wettergren, A.; Larsen, P.N.; Rasmussen, A.

    2008-01-01

    of hepatic metastases from colorectal cancer and hepatocellular carcinoma in our institution. MATERIALS AND METHODS: The patients who underwent their primary liver resection from 1.1.1995-31.12.2004 in our institution were included. The surgical outcome was reviewed retrospectively and the five-year survival...... after resection of hepatic metastases from colorectal cancer and hepatocellular carcinoma was estimated. RESULTS: 141 patients (71M/70F), median age 58 years (1-78), underwent a liver resection in the ten-year period. The number of resections increased from two in 1995 to 32 in 2004. Median hospital...

  18. Minilaparoscopic Colorectal Resections: Technical Note

    Directory of Open Access Journals (Sweden)

    S. Bona

    2012-01-01

    Full Text Available Laparoscopic colorectal resections have been shown to provide short-term advantages in terms of postoperative pain, general morbidity, recovery, and quality of life. To date, long-term results have been proved to be comparable to open surgery irrefutably only for colon cancer. Recently, new trends keep arising in the direction of minimal invasiveness to reduce surgical trauma after colorectal surgery in order to improve morbidity and cosmetic results. The few reports available in the literature on single-port technique show promising results. Natural orifices endoscopic techniques still have very limited application. We focused our efforts in standardising a minilaparoscopic technique (using 3 to 5 mm instruments for colorectal resections since it can provide excellent cosmetic results without changing the laparoscopic approach significantly. Thus, there is no need for a new learning curve as minilaparoscopy maintains the principle of instrument triangulation. This determines an undoubted advantage in terms of feasibility and reproducibility of the procedure without increasing operative time. Some preliminary experiences confirm that minilaparoscopic colorectal surgery provides acceptable results, comparable to those reported for laparoscopic surgery with regard to operative time, morbidity, and hospital stay. Randomized controlled studies should be conducted to confirm these early encouraging results.

  19. Effect of season on peripheral resistance to localised cold stress

    Science.gov (United States)

    Tanaka, M.; Harimura, Y.; Tochihara, Y.; Yamazaki, S.; Ohnaka, T.; Matsui, J.; Yoshida, K.

    1984-03-01

    This study was carried out to determine the effect that seasonal changes have on the effect of localised cold stress on peripheral temperatures using the foot immersion method with a cold water bath. The subjects were six males and four females. The data were obtained in April, July, October and January. Skin temperature of the right index finger, the forehead, the arm, the cheek, the second toe and the instep were measured before, during and after the immersion of the feet in water at 15°C for 10 mins, as well as oxygen consumption before immersion of the feet. The average finger temperature was highest during foot immersion in the summer, next highest in the winter, then spring, and the lowest during foot immersion in the autumn. The finger temperatures during the pre-immersion period in the autumn tended to be lower than in other seasons. The finger temperatures during the pre-immersion period affected the temperature change of the finger during the immersion period. The rate of increase of the toe temperature and the foot temperature during post-immersion in the summer and the spring were greater than those in the autumn and winter. Oxygen consumption during the pre-immersion period in the autumn was significantly lower than in the other seasons (pCooling the feet caused no significant changes in the temperatures the cheek, forehead or forearm. The cheek temperature in the summer and autumn was cooler than corresponding temperatures taken in the winter and spring.

  20. The Competition Between a Localised and Distributed Source of Buoyancy

    Science.gov (United States)

    Partridge, Jamie; Linden, Paul

    2012-11-01

    We propose a new mathematical model to study the competition between localised and distributed sources of buoyancy within a naturally ventilated filling box. The main controlling parameters in this configuration are the buoyancy fluxes of the distributed and local source, specifically their ratio Ψ. The steady state dynamics of the flow are heavily dependent on this parameter. For large Ψ, where the distributed source dominates, we find the space becomes well mixed as expected if driven by an distributed source alone. Conversely, for small Ψ we find the space reaches a stable two layer stratification. This is analogous to the classical case of a purely local source but here the lower layer is buoyant compared to the ambient, due to the constant flux of buoyancy emanating from the distributed source. The ventilation flow rate, buoyancy of the layers and also the location of the interface height, which separates the two layer stratification, are obtainable from the model. To validate the theoretical model, small scale laboratory experiments were carried out. Water was used as the working medium with buoyancy being driven directly by temperature differences. Theoretical results were compared with experimental data and overall good agreement was found. A CASE award project with Arup.

  1. Antenna array geometry optimization for a passive coherent localisation system

    Science.gov (United States)

    Knott, Peter; Kuschel, Heiner; O'Hagan, Daniel

    2012-11-01

    Passive Coherent Localisation (PCL), also known as Passive Radar, making use of RF sources of opportunity such as Radio or TV Broadcasting Stations, Cellular Phone Network Base Stations, etc. is an advancing technology for covert operation because no active radar transmitter is required. It is also an attractive addition to existing active radar stations because it has the potential to discover low-flying and low-observable targets. The CORA (Covert Radar) experimental passive radar system currently developed at Fraunhofer-FHR features a multi-channel digital radar receiver and a circular antenna array with separate elements for the VHF- and the UHF-range and is used to exploit alternatively Digital Audio (DAB) or Video Broadcasting (DVB-T) signals. For an extension of the system, a wideband antenna array is being designed for which a new discone antenna element has been developed covering the full DVB-T frequency range. The present paper describes the outline of the system and the numerical modelling and optimisation methods applied to solve the complex task of antenna array design: Electromagnetic full wave analysis is required for the parametric design of the antenna elements while combinatorial optimization methods are applied to find the best array positions and excitation coefficients for a regular omni-directional antenna performance. The different steps are combined in an iterative loop until the optimum array layout is found. Simulation and experimental results for the current system will be shown.

  2. Le kyste hydatique du cordon spermatique: une localisation exceptionnelle

    Science.gov (United States)

    Hamdane, Mohamed Moncef; Bougrine, Fethi; Msakni, Issam; Dhaoui-Ghozzi, Amen; Bouziani, Ammar

    2011-01-01

    L’ hydatidose est une anthropo-zoonose due au développement chez l'homme de la forme larvaire du taenia Echinococcus granulosis. La plupart des kystes hydatiques se localisent dans le foie et les poumons. Le kyste hydatique du cordon spermatique est extrêmement rare avec seulement 4 cas rapportés dans la littérature. Les auteurs rapportent dans cet article un nouveau cas d'hydatidose du cordon spermatique. Il s'agissait d'un homme de 40 ans qui consultait pour des douleurs scrotales évoluant depuis huit mois. L'examen clinique a mis en évidence une tuméfaction mobile, inguino-scrotale, droite. L’échographie testiculaire a objectivé une hernie inguinale droite associée à deux kystes épididymaires bilatéraux. Le patient a été opéré pour cure de son hernie avec découverte en per-opératoire d'un kyste du cordon spermatique qui a été réséqué. L'examen anatomopathologique a conclu à une hydatidose du cordon spermatique. PMID:22384304

  3. The instability of internal gravity waves to localised disturbances

    Directory of Open Access Journals (Sweden)

    J. Vanneste

    1995-02-01

    Full Text Available The instability of an internal gravity wave due to nonlinear wave-wave interaction is studied theoretically and numerically. Three different aspects of this phenomenon are examined. 1. The influence of dissipation on both the resonant and the nonresonant interactions is analysed using a normal mode expansion of the basic equations. In particular, the modifications induced in the interaction domain are calculated and as a result some modes are shown to be destabilised by dissipation. 2. The evolution of an initial unstable disturbance of finite vertical extent is described as the growth of two secondary wave packets travelling at the same group velocity. A quasi-linear correction to the basic primary wave is calculated, corresponding to a localised amplitude decrease due to the disturbance growth. 3. Numerical experiments are carried out to study the effect of a basic shear on wave instability. It appears that the growing secondary waves can have a frequency larger than that of the primary wave, provided that the shear is sufficient. The instability of waves with large amplitude and long period, such as tides or planetary waves, could therefore be invoked as a possible mechanism for the generation of gravity waves with shorter period in the middle atmosphere.

  4. Newly-derived neuroblastoma cell lines propagated in serum-free media recapitulate the genotype and phenotype of primary neuroblastoma tumours.

    Science.gov (United States)

    Bate-Eya, Laurel T; Ebus, Marli E; Koster, Jan; den Hartog, Ilona J M; Zwijnenburg, Danny A; Schild, Linda; van der Ploeg, Ida; Dolman, M Emmy M; Caron, Huib N; Versteeg, Rogier; Molenaar, Jan J

    2014-02-01

    Recently protocols have been devised for the culturing of cell lines from fresh tumours under serum-free conditions in defined neural stem cell medium. These cells, frequently called tumour initiating cells (TICs) closely retained characteristics of the tumours of origin. We report the isolation of eight newly-derived neuroblastoma TICs from six primary neuroblastoma tumours and two bone marrow metastases. The primary tumours from which these TICs were generated have previously been fully typed by whole genome sequencing (WGS). Array comparative genomic hybridisation (aCGH) analysis showed that TIC lines retained essential characteristics of the primary tumours and exhibited typical neuroblastoma chromosomal aberrations such as MYCN amplification, gain of chromosome 17q and deletion of 1p36. Protein analysis showed expression for neuroblastoma markers MYCN, NCAM, CHGA, DBH and TH while haematopoietic markers CD19 and CD11b were absent. We analysed the growth characteristics and confirmed tumour-forming potential using sphere-forming assays, subcutaneous and orthotopic injection of these cells into immune-compromised mice. Affymetrix mRNA expression profiling of TIC line xenografts showed an expression pattern more closely mimicking primary tumours compared to xenografts from classical cell lines. This establishes that these neuroblastoma TICs cultured under serum-free conditions are relevant and useful neuroblastoma tumour models. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. Interleukin-24 induces neuroblastoma SH-SY5Y cell differentiation, growth inhibition, and apoptosis by promoting ROS production.

    Science.gov (United States)

    Li, Yuan; Zhang, Hongwei; Zhu, Xiaoyu; Feng, Dongchuan; Gong, Jinchao; Han, Tao

    2013-11-01

    Neuroblastoma is among the most aggressive tumors that occur in childhood and infancy. The clinical prognosis of children with advanced-stage neuroblastoma is still poor. Interleukin-24 (IL-24) is emerging as a new cytokine involved in tumor cellular proliferation, differentiation, and apoptosis and has been widely studied as a tumor inhibitor. However, little is known about this cytokine's role in neuroblastoma. In this study, we investigated the possible effects of IL-24 on inducing neuroblastoma cell differentiation, growth inhibition, and apoptosis in vitro. Our data show that IL-24 promotes neuroblastoma SH-SY5Y cell differentiation, growth inhibition, and apoptosis. Furthermore, we found that the differentiation- and apoptosis-inducing action of IL-24 depends on the accumulation of reactive oxygen species (ROS). These results suggest that IL-24 can induce neuroblastoma cell differentiation and apoptosis and may be a potential therapeutic agent for neuroblastoma.

  6. Which patients with resectable pancreatic cancer truly benefit from oncological resection: is it destiny or biology?

    Science.gov (United States)

    Zheng, Lei; Wolfgang, Christopher L

    2015-01-01

    Pancreatic cancer has a dismal prognosis. A technically perfect surgical operation may still not provide a survival advantage for patients with technically resectable pancreatic cancer. Appropriate selection of patients for surgical resections is an imminent issue. Recent studies have provided an important clue on what serum biomarkers may be used to select out the patients who would unlikely benefit from the surgical resection.

  7. Clipping of tumour resection margins allows accurate target volume delineation in head and neck cancer adjuvant radiation therapy

    International Nuclear Information System (INIS)

    Bittermann, Gido; Wiedenmann, Nicole; Bunea, Andrei; Schwarz, Steffen J.; Grosu, Anca-L.; Schmelzeisen, Rainer; Metzger, Marc C.

    2015-01-01

    Background: Accurate tumour bed localisation is a key requirement for adjuvant radiotherapy. A new procedure is described for head and neck cancer treatment that improves tumour bed localisation using titanium clips. Materials and methods: Following complete local excision of the primary tumour, the tumour bed was marked with titanium clips. Preoperative gross target volume (GTV) and postoperative tumour bed were examined and the distances between the centres of gravity were evaluated. Results: 49 patients with squamous cell carcinoma of the oral cavity were prospectively enrolled in this study. All patients underwent tumour resection, neck lymph node dissection and defect reconstruction in one stage. During surgery, 7–49 clips were placed in the resection cavity. Surgical clip insertion was successful in 88% (n = 43). Clip identification and tumour bed delineation was successful in all 43 patients. The overall distance between the centres of gravity of the preoperative tumour extension to the tumour bed was 0.9 cm. A significant relationship between the preoperative tumour extension and the postoperative tumour bed volume could be demonstrated. Conclusion: We demonstrate a precise delineation of the former tumour cavity. Improvements in tumour bed delineation allow an increase of accuracy for adjuvant treatment

  8. An Efficient Approach for Node Localisation and Tracking in Wireless Sensor Networks

    CSIR Research Space (South Africa)

    Mwila, Martin

    2014-08-01

    Full Text Available -1 An Efficient Approach for Node Localisation and Tracking in Wireless Sensor Networks Martin K. Mwila Submitted in partial fulfilment of the requirements for the degree Magister Technologiae: Electrical Engineering in the Department of Electrical Engineering...

  9. An efficient distributed localisation algorithm for wireless sensor networks: based on smart reference-selection method

    CSIR Research Space (South Africa)

    Abu-Mahfouz, Adnan M

    2013-05-01

    Full Text Available Determining the location of nodes is a key part of wireless sensor networks (WSNs). Many WSN applications require knowledge of nodes’ locations to perform their functions successfully. Several localisation algorithms rely on using all or most...

  10. Electron localisation in static and time-dependent one-dimensional model systems

    Science.gov (United States)

    Durrant, T. R.; Hodgson, M. J. P.; Ramsden, J. D.; Godby, R. W.

    2018-02-01

    The most direct signature of electron localisation is the tendency of an electron in a many-body system to exclude other same-spin electrons from its vicinity. By applying this concept directly to the exact many-body wavefunction, we find that localisation can vary considerably between different ground-state systems, and can also be strongly disrupted, as a function of time, when a system is driven by an applied electric field. We use this measure to assess the well-known electron localisation function (ELF), both in its approximate single-particle form (often applied within density-functional theory) and its full many-particle form. The full ELF always gives an excellent description of localisation, but the approximate ELF fails in time-dependent situations, even when the exact Kohn-Sham orbitals are employed.

  11. Association of telomerase activity with radio- and chemosensitivity of neuroblastomas

    Directory of Open Access Journals (Sweden)

    Willich Normann

    2010-07-01

    Full Text Available Abstract Background Telomerase activity compensates shortening of telomeres during cell division and enables cancer cells to escape senescent processes. It is also supposed, that telomerase is associated with radio- and chemoresistance. In the here described study we systematically investigated the influence of telomerase activity (TA and telomere length on the outcome of radio- and chemotherapy in neuroblastoma. Methods We studied the effects on dominant negative (DN mutant, wild type (WT of the telomerase catalytic unit (hTERT using neuroblastoma cell lines. The cells were irradiated with 60Co and treated with doxorubicin, etoposide, cisplatin and ifosfamide, respectively. Viability was determined by MTS/MTT-test and the GI50 was calculated. Telomere length was measured by southernblot analysis and TA by Trap-Assay. Results Compared to the hTERT expressing cells the dominant negative cells showed increased radiosensitivity with decreased telomere length. Independent of telomere length, telomerase negative cells are significantly more sensitive to irradiation. The effect of TA knock-down or overexpression on chemosensitivity were dependent on TA, the anticancer drug, and the chemosensitivity of the maternal cell line. Conclusions Our results supported the concept of telomerase inhibition as an antiproliferative treatment approach in neuroblastomas. Telomerase inhibition increases the outcome of radiotherapy while in combination with chemotherapy the outcome depends on drug- and cell line and can be additive/synergistic or antagonistic. High telomerase activity is one distinct cancer stem cell feature and the here described cellular constructs in combination with stem cell markers like CD133, Aldehyddehydrogenase-1 (ALDH-1 or Side population (SP may help to investigate the impact of telomerase activity on cancer stem cell survival under therapy.

  12. Hypertension complicating 131I-meta-iodobenzylguanidine therapy for neuroblastoma

    International Nuclear Information System (INIS)

    Kosmin, Michael A.; Cork, Nicholas J.; Gaze, Mark N.; Bomanji, Jamshed B.; Shankar, Ananth

    2012-01-01

    Radiolabelled meta-iodobenzylguanidine (mIBG), used as targeted therapy for neuroblastoma, is known to have effects on blood pressure (BP). In this study we audited BP changes in patients receiving 131 I-mIBG therapy for neuroblastoma to identify BP-related adverse events (AE) and possible predictive factors. Between 2003 and 2010, 50 patients with neuroblastoma received 110 131 I-mIBG administrations. BP measurements before and after administration were compared with age- and sex-matched centile values. AE were analysed, and possible predisposing factors identified. This population had a baseline BP distribution higher than that of their age- and sex-matched peers, with 16% of preadministration systolic BP values above the 95th centile. Changes in BP after administration showed an approximately normal distribution with similar numbers of reduced and increased values. Four AE, all related to hypertension, occurred with one patient having generalized seizures. One AE was immediate, others occurred between 20 and 25 h after administration. No significant association between AE and patient age or sex was demonstrated. However, a significant association between AE and high preadministration BP was shown, both above the 90th centile (p = 0.0022) and above the 95th centile (p = 0.0135). Clinically relevant hypertension following 131 I-mIBG therapy affected less than 5% of administrations, but was more common in those patients with preexisting hypertension. As hypertensive episodes may occur many hours after treatment, close monitoring of BP needs to be continued for at least 48 h after administration of 131 I-mIBG. (orig.)

  13. Immunohistochemical evaluation of molecular radiotherapy target expression in neuroblastoma tissue

    Energy Technology Data Exchange (ETDEWEB)

    Gains, Jennifer E.; Gaze, Mark N. [University College London Hospitals NHS Foundation Trust, Department of Oncology, London (United Kingdom); Sebire, Neil J. [Great Ormond Street Hospital for Children NHS Foundation Trust, Department of Pathology, London (United Kingdom); Moroz, Veronica; Wheatley, Keith [University of Birmingham, Cancer Research UK Clinical Trials Unit, Birmingham (United Kingdom)

    2018-03-15

    Neuroblastoma may be treated with molecular radiotherapy, {sup 131}I meta-Iodobenzylguanidine and {sup 177}Lu Lutetium DOTATATE, directed at distinct molecular targets: Noradrenaline Transporter Molecule (NAT) and Somatostatin Receptor (SSTR2), respectively. This study used immunohistochemistry to evaluate target expression in archival neuroblastoma tissue, to determine whether it might facilitate clinical use of molecular radiotherapy. Tissue bank samples of formalin fixed paraffin embedded neuroblastoma tissue from patients for whom clinical outcome data were available were sectioned and stained with haematoxylin and eosin, and monoclonal antibodies directed against NAT and SSTR2. Sections were examined blinded to clinical information and scored for the percentage and intensity of tumour cells stained. These data were analysed in conjunction with clinical data. Tissue from 75 patients was examined. Target expression scores varied widely between patients: NAT median 45%, inter-quartile range 25% - 65%; and SSTR2 median 55%, interquartile range 30% - 80%; and in some cases heterogeneity of expression between different parts of a tumour was observed. A weak positive correlation was observed between the expression scores of the different targets: correlation coefficient = 0.23, p = 0.05. MYCN amplified tumours had lower SSTR2 scores: mean difference 23% confidence interval 8% - 39%, p < 0.01. Survival did not differ by scores. As expression of both targets is variable and heterogeneous, imaging assessment of both may yield more clinical information than either alone. The clinical value of immunohistochemical assessment of target expression requires prospective evaluation. Variable target expression within a patient may contribute to treatment failure. (orig.)

  14. Treatment of neuroblastoma. Role of total Body Irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Dini, G; Perin, G P; Franzone, P; Corvo, R; Scarpati, D

    1986-01-01

    Advanced neuroblastoma, scarcely responsive to conventional therapies, can take advantage of high dose chemio-radiotherapic treatment followed by bone marrow transplant. Nineteen young patients underwent an ablative chemotherapy with high dose Vincristine and Melphalan plus Total Body Irradiation in Genoa, Italy; all of them underwent autologus bone marrow transplantation. Fourteen children were in complete remission (CR), 5 had residual disease. Thirteen are alive after a median of 7 months following transplant; 9 are in CR; 4 have disease; 1 died for toxicity; 5 for relapse. The results seem to suggest that ablative therapy should be given to patients in CR. Toxicity was not remarkable mainly as far as TBI is concerned.

  15. Leakage localisation method in a water distribution system based on sensitivity matrix: methodology and real test

    OpenAIRE

    Pascual Pañach, Josep

    2010-01-01

    Leaks are present in all water distribution systems. In this paper a method for leakage detection and localisation is presented. It uses pressure measurements and simulation models. Leakage localisation methodology is based on pressure sensitivity matrix. Sensitivity is normalised and binarised using a common threshold for all nodes, so a signatures matrix is obtained. A pressure sensor optimal distribution methodology is developed too, but it is not used in the real test. To validate this...

  16. Biliary Stricture Following Hepatic Resection

    Directory of Open Access Journals (Sweden)

    Jeffrey B. Matthews

    1991-01-01

    Full Text Available Anatomic distortion and displacement of hilar structures due to liver lobe atrophy and hypertrophy occasionally complicates the surgical approach for biliary stricture repair. Benign biliary stricture following hepatic resection deserves special consideration in this regard because the inevitable hypertrophy of the residual liver causes marked rotation and displacement of the hepatic hilum that if not anticipated may render exposure for repair difficult and dangerous. Three patients with biliary stricture after hepatectomy illustrate the influence of hepatic regeneration on attempts at subsequent stricture repair. Following left hepatectomy, hypertrophy of the right and caudate lobes causes an anteromedial rotation and displacement of the portal structures. After right hepatectomy, the rotation is posterolateral, and a thoracoabdominal approach may be necessary for adequate exposure. Radiographs obtained in the standard anteroposterior projection may be deceptive, and lateral views are recommended to aid in operative planning.

  17. Distinguishing neuroblastoma invading the kidney from nephroblastoma: evaluation in computed tomography

    International Nuclear Information System (INIS)

    Qiao Zhongwei; Li Guoping; Mamier; Wang Kang'an; Lv Zhibao; Miao Fei

    2005-01-01

    Objective: To evaluate the CT findings in the differential diagnosis between neuroblastoma invading the kidney and nephroblastoma. Methods: CT morphologic details in 13 patients with neuroblastoma invading the kidney confirmed by surgical operation and pathology were studied, and CT findings in 15 patients with nephroblastoma confirmed by surgery and pathology were compared. Results: In 13 cases of neuroblastoma, CT showed irregular mass in 12 cases, tumor with poorly defined margins in 11 cases, tumorous calcifications in 10 cases, invasion of retroperitoneal vessels in 9 cases, and retroperitoneal and retrocrural lymph nodes invasion in 12 cases. In 15 cases of nephroblastoma, round mass was p resented in 12 cases, tumor with poorly defined margins in 2 cases, tumorous calcifications in 2 cases, involvement of retroperitoneal vessels in 2 cases, and invasion of retroperitoneal lymph nodes in 3 cases. None of the nephroblastoma invaded retrocrural lymph nodes. Irregular mass with calcifications, involvement of retroperitoneal vessels, retrocrural and retroperitoneal lymph nodes were more common in cases of neuroblastoma than in nephroblastoma. Moreover, involvement of retrocrural lymph nodes and encasement of retroperitoneal vessels had higher positive prediction value on neuroblastoma. Conclusion: Involvement of retrocrural lymph nodes and encasement of retroperitoneal vessels were the specific CT findings of neuroblastoma and the most valuable evidence in distinguishing neuroblastoma from nephroblastoma. (authors)

  18. Clinical experiences in the treatment of neuroblastoma with 131I-metaiodobenzylguanidine

    International Nuclear Information System (INIS)

    Treuner, J.; Klingebiel, T.; Feine, U.; Buck, J.; Bruchelt, G.; Dopfer, R.; Girgert, R.; Mueller-Schauenburg, W.M.; Meinke, J.; Kaiser, W.

    1986-01-01

    Treatment of neuroblastoma is an unsolved problem of pediatric oncology. In spite of highly intensified chemotherapy, the long-term survival rate of children with a metastatic neuroblastoma is below 10%. We therefore used 131 I-metaiodobenzylguanidine (MIBG) for the first time to treat children with a neuroblastoma in relapse or primary unresponsiveness to chemotherapy. We had previously demonstrated that MIBG is useful for the scintigraphic imaging of neuroblastoma lesions and had investigated the cytotoxicity and uptake of MIBG in various neuroblastoma cell lines. We treated 6 children with neuroblastoma in a total of 19 courses. Three of the children suffered from a relapse of neuroblastoma; 3 had never gained a remission. Four of the 6 children lost their bone pain and fever during the first 3 days. In 5 of the 6 children the solid tumor as well as the bone marrow infiltration responded to MIBG treatment, with responses ranging from transitory decrease of the tumor mass to complete disappearance of abdominal tumors. We also witnessed a stabilization of osteolytic lesions, a decrease in elevated serum catecholamines, and a decrease in bone marrow infiltration. Five of the 6 children died of tumor progression 55-249 days after the first MIBG treatment

  19. Neuroblastoma arginase activity creates an immunosuppressive microenvironment that impairs autologous and engineered immunity

    Science.gov (United States)

    Mussai, Francis; Egan, Sharon; Hunter, Stuart; Webber, Hannah; Fisher, Jonathan; Wheat, Rachel; McConville, Carmel; Sbirkov, Yordan; Wheeler, Kate; Bendle, Gavin; Petrie, Kevin; Anderson, John; Chesler, Louis; De Santo, Carmela

    2015-01-01

    Neuroblastoma is the most common extra cranial solid tumour of childhood, and survival remains poor for patients with advanced disease. Novel immune therapies are currently in development, but clinical outcomes have not matched preclinical results. Here, we describe key mechanisms in which neuroblastoma inhibits the immune response. We show that murine and human neuroblastoma tumour cells suppress T cell proliferation, through increased arginase activity. Arginase II is the predominant isoform expressed and creates an arginine deplete local and systemic microenvironment. Neuroblastoma arginase activity results in inhibition of myeloid cell activation and suppression of bone marrow CD34+ progenitor proliferation. Finally we demonstrate that the arginase activity of neuroblastoma impairs NY-ESO-1 specific TCR and GD2-specific CAR engineered T cell proliferation and cytotoxicity. High arginase II expression correlates with poor survival for neuroblastoma patients. The results support the hypothesis that neuroblastoma creates an arginase-dependent immunosuppressive microenvironment in both the tumour and blood that leads to impaired immune surveillance and sub-optimal efficacy of immunotherapeutic approaches. PMID:26054597

  20. Gene expression profiling in response to the histone deacetylase inhibitor BL1521 in neuroblastoma

    International Nuclear Information System (INIS)

    Ruijter, Annemieke J.M. de; Meinsma, Rutger J.; Bosma, Peter; Kemp, Stephan; Caron, Huib N.; Kuilenburg, Andre B.P. van

    2005-01-01

    Neuroblastoma is a childhood tumor with a poor survival in advanced stage disease despite intensive chemotherapeutic regimes. The new histone deacetylase (HDAC) inhibitor BL1521 has shown promising results in neuroblastoma. Inhibition of HDAC resulted in a decrease in proliferation and metabolic activity, induction of apoptosis and differentiation of neuroblastoma cells. In order to elucidate the mechanism mediating the effects of BL1521 on neuroblastoma cells, we investigated the gene expression profile of an MYCN single copy (SKNAS) and an MYCN amplified (IMR32) neuroblastoma cell line after treatment with BL1521 using the Affymetrix oligonucleotide array U133A. An altered expression of 255 genes was observed in both neuroblastoma cell lines. The majority of these genes were involved in gene expression, cellular metabolism, and cell signaling. We observed changes in the expression of vital genes belonging to the cell cycle (cyclin D1 and CDK4) and apoptosis (BNIP3, BID, and BCL2) pathway in response to BL1521. The expression of 37 genes was altered by both BL1521 and Trichostatin A, which could indicate a common gene set regulated by different HDAC inhibitors. BL1521 treatment changed the expression of a number of MYCN-associated genes. Several genes in the Wnt and the Delta/Notch pathways were changed in response to BL1521 treatment, suggesting that BL1521 is able to induce the differentiation of neuroblastoma cells into a more mature phenotype

  1. Approaches to open quantum systems: Decoherence, localisation and all that

    International Nuclear Information System (INIS)

    Yu Ting

    1998-01-01

    This thesis is mainly concerned with issues in quantum open systems and the foundations of quantum theory. Chapter I introduces the aim, background and main results which take place in the following chapters. Chapters II and III are used to study and compare the decoherent histories approach, the environment-induced decoherence and the localisation properties of the solutions to the stochastic Schrodinger equation in quantum jump simulation and quantum state diffusion approaches, for a quantum two-level system model. We show, in particular, that there is a close connection between the decoherent histories and the quantum jump simulation, complementing a connection with the quantum state diffusion approach noted earlier by Diosi, Gisin, Halliwell and Percival. In the case of the decoherent histories analysis, the degree of approximate decoherence is discussed in detail. As by-product, by using the von Neumann entropy, we also discuss the predictability and its relation to the upper bounds of degree of decoherence. In Chapter IV, we give an alternative and elementary derivation of the Hu-Paz-Ghang master equation for quantum Brownian motion in a general environment, which involves tracing the evolution equation for the Wigner function. We also discuss the master equation in some special cases. This master equation provides a very useful tool to study the decoherence of a quantum system due to the interaction with its environment. In Chapter V, a derivation of the parameter-based uncertainty relation between position and momentum is given. This uncertainty relation can be regarded as an exact counterpart of the time-energy uncertainty relation. The final chapter is a rather brief summary of the thesis. (author)

  2. Initial Australian experience with daily ultrasound localisation for prostate radiotherapy

    International Nuclear Information System (INIS)

    Kneebone, A.; Fuller, M.W.; Williams, M.J.

    2003-01-01

    Variability in prostate position is a major problem in the delivery of external beam radiotherapy (EBRT). Daily ultrasound localisation prior to radiotherapy has become popular in the United States but to date has not been used clinically in Australia or New Zealand. Daily transabdominal ultrasound images through the prostate were acquired using the BAT ultrasound system. Contour data from the planning system is reconstructed at the same locations/angles as the BAT images. By overlaying the planned contours with the newly acquired images, the isocentre is adjusted to ensure that the prostate will be within the irradiated volume. After commissioning by Medical Physics, an initial pre-clinical trial period was adopted. This involved performing BAT alignments daily but treating to the planned isocentre in 30 patients. Eighty three percent of patients (25/30) had images judged to be of good or excellent quality by the reviewing radiation oncologist. It was noted that for each operator there was a period needed to build confidence/competence in both imaging and interpreting the images for the moves. The median scan time in addition to the normal patient set-up was 3.2 minutes (range=1.5-12.0 mins) with the second 15 patients scanned quicker than the first 15 (2.9 minutes versus 3.8 minutes). A summary of the movements recommended by the BAT system is contained in the table. We feel that daily prostate ultrasound localization offers a significant advance in delivering EBRT for prostate cancer. The incorporation of the system into clinical use, however, was not without difficulty and requires significant time and effort from therapists, physicists and medical staff. Further clinical evaluation of the unit is ongoing

  3. Localised uptake and extraction of calcium45 in dinoflagellate nuclei

    International Nuclear Information System (INIS)

    Sigee, D.C.

    1983-01-01

    The uptake of Ca 45 into cells of the dinoflagellate Glenodinium foliaceum was investigated using insoluble compound light microscope autoradiography. The distribution of silver grains showed marked localisation to the dinocaryotic nucleus, with a random scatter of grains over the surrounding protoplasm (cytoplasm and supernumerary nucleus). Correction of grain counts for lateral sensitisation from the dinocaryotic nucleus indicated an isotope concentration 16 32 times greater in this organelle compared to the rest of the cell. Cells labelled for varying periods of time showed differences in the pattern of Ca 45 uptake throughout the sample populations, but no increase in the mean level of uptake per cell. This would suggest a rapid incorporation of isotope within 1-2 hours, with little subsequent uptake. The presence of high levels of label after processing with both additive (glutaraldehyde, paraformaldehyde) and coagulative (acetic alcohol) fixatives indicated that the retention of Ca 45 in these preparations was not simply a fixation artefact. Although the isotope did not appear to be suitable for (high resolution) electron microscope autoradiography, the intranuclear site of incorporation was demonstrated indirectly using a buffer extraction technique. Prolonged treatment with phosphate buffer resulted in a large scale loss of label from both cytoplasm and dinocaryotic nucleus. The latter appeared to show specific correlation with the loss of (protein) matrix from the chromosomes - as observed under both light and electron microscopy, with no apparent change in either nucleolus or nucleoplasm. This would suggest that incorporated Ca 45 in the nucleus was largely confined to the condensed chromatin, where it was combined with the acidic proteins which make up the bulk of the chromatin matrix. The results obtained in this investigation are related to previous studies involving X-ray microanalysis and uptake of Ni 63 . (Author)

  4. The resection angle in apical surgery

    DEFF Research Database (Denmark)

    von Arx, Thomas; Janner, Simone F M; Jensen, Simon S

    2016-01-01

    OBJECTIVES: The primary objective of the present radiographic study was to analyse the resection angle in apical surgery and its correlation with treatment outcome, type of treated tooth, surgical depth and level of root-end filling. MATERIALS AND METHODS: In the context of a prospective clinical...... study, cone beam computed tomography (CBCT) scans were taken before and 1 year after apical surgery to measure the angle of the resection plane relative to the longitudinal axis of the root. Further, the surgical depth (distance from the buccal cortex to the most lingual/palatal point of the resection...... or with the retrofilling length. CONCLUSIONS: Statistically significant differences were observed comparing resection angles of different tooth groups. However, the angle had no significant effect on treatment outcome. CLINICAL RELEVANCE: Contrary to common belief, the resection angle in maxillary anterior teeth...

  5. Selective elimination of neuroblastoma cells by synergistic effect of Akt kinase inhibitor and tetrathiomolybdate.

    Science.gov (United States)

    Navrátilová, Jarmila; Karasová, Martina; Kohutková Lánová, Martina; Jiráková, Ludmila; Budková, Zuzana; Pacherník, Jiří; Šmarda, Jan; Beneš, Petr

    2017-09-01

    Neuroblastoma is the most common extracranial solid tumour of infancy. Pathological activation of glucose consumption, glycolysis and glycolysis-activating Akt kinase occur frequently in neuroblastoma cells, and these changes correlate with poor prognosis of patients. Therefore, several inhibitors of glucose utilization and the Akt kinase activity are in preclinical trials as potential anti-cancer drugs. However, metabolic plasticity of cancer cells might undermine efficacy of this approach. In this work, we identified oxidative phosphorylation as compensatory mechanism preserving viability of neuroblastoma cells with inhibited glucose uptake/Akt kinase. It was oxidative phosphorylation that maintained intracellular level of ATP and proliferative capacity of these cells. The oxidative phosphorylation inhibitors (rotenone, tetrathiomolybdate) synergized with inhibitor of the Akt kinase/glucose uptake in down-regulation of both viability of neuroblastoma cells and clonogenic potential of cells forming neuroblastoma spheroids. Interestingly, tetrathiomolybdate acted as highly specific inhibitor of oxygen consumption and activator of lactate production in neuroblastoma cells, but not in normal fibroblasts and neuronal cells. Moreover, the reducing effect of tetrathiomolybdate on cell viability and the level of ATP in the cells with inhibited Akt kinase/glucose uptake was also selective for neuroblastoma cells. Therefore, efficient elimination of neuroblastoma cells requires inhibition of both glucose uptake/Akt kinase and oxidative phosphorylation activities. The use of tetrathiomolybdate as a mitochondrial inhibitor contributes to selectivity of this combined treatment, preferentially targeting neuroblastoma cells. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  6. Tissue factor/FVIIa activates Bcl-2 and prevents doxorubicin-induced apoptosis in neuroblastoma cells

    International Nuclear Information System (INIS)

    Fang, Jun; Gu, Lubing; Zhu, Ningxi; Tang, Hao; Alvarado, Carlos S; Zhou, Muxiang

    2008-01-01

    Tissue factor (TF) is a transmembrane protein that acts as a receptor for activated coagulation factor VII (FVIIa), initiating the coagulation cascade. Recent studies demonstrate that expression of tumor-derived TF also mediates intracellular signaling relevant to tumor growth and apoptosis. Our present study investigates the possible mechanism by which the interaction between TF and FVIIa regulates chemotherapy resistance in neuroblastoma cell lines. Gene and siRNA transfection was used to enforce TF expression in a TF-negative neuroblastoma cell line and to silence endogenous TF expression in a TF-overexpressing neuroblastoma line, respectively. The expression of TF, Bcl-2, STAT5, and Akt as well as the phosphorylation of STAT5 and Akt in gene transfected cells or cells treated with JAK inhibitor and LY294002 were determined by Western blot assay. Tumor cell growth was determined by a clonogenic assay. Cytotoxic and apoptotic effect of doxorubicin on neuroblastoma cell lines was analyzed by WST assay and annexin-V staining (by flow cytometry) respectively. Enforced expression of TF in a TF-negative neuroblastoma cell line in the presence of FVIIa induced upregulation of Bcl-2, leading to resistance to doxorubicin. Conversely, inhibition of endogenous TF expression in a TF-overexpressing neuroblastoma cell line using siRNA resulted in down-regulation of Bcl-2 and sensitization to doxorubicin-induced apoptosis. Additionally, neuroblastoma cells expressing high levels of either endogenous or transfected TF treated with FVIIa readily phosphorylated STAT5 and Akt. Using selective pharmacologic inhibitors, we demonstrated that JAK inhibitor I, but not the PI3K inhibitor LY294002, blocked the TF/FVIIa-induced upregulation of Bcl-2. This study shows that in neuroblastoma cell lines overexpressed TF ligated with FVIIa produced upregulation of Bcl-2 expression through the JAK/STAT5 signaling pathway, resulting in resistance to apoptosis. We surmise that this TF

  7. Safe Resection and Primary Anastomosis of Gangrenous Sigmoid ...

    African Journals Online (AJOL)

    %) of the sigmoid volvulus was gangrenous and 85.2% of all the sigmoid volvulus was managed by resection and primary anastomosis. Complications seen after resection and primary anastomosis were anastomotic leak at 4.5%, resection.

  8. Neuroblastoma mRNAs predict outcome in children with stage 4 neuroblastoma: a European HR-NBL1/SIOPEN study.

    Science.gov (United States)

    Viprey, Virginie F; Gregory, Walter M; Corrias, Maria V; Tchirkov, Andrei; Swerts, Katrien; Vicha, Ales; Dallorso, Sandro; Brock, Penelope; Luksch, Roberto; Valteau-Couanet, Dominique; Papadakis, Vassilios; Laureys, Genevieve; Pearson, Andrew D; Ladenstein, Ruth; Burchill, Susan A

    2014-04-01

    To evaluate the hypothesis that detection of neuroblastoma mRNAs by reverse transcriptase quantitative polymerase chain reaction (RTqPCR) in peripheral blood (PB) and bone marrow aspirates (BM) from children with stage 4 neuroblastoma are clinically useful biomarkers of risk. RTqPCR for paired-like homeobox 2b (PHOX2B), tyrosine hydroxylase (TH), and doublecortin (DCX) mRNA in PB and BM of children enrolled onto the High-Risk Neuroblastoma Trial-1 of the European Society of Pediatric Oncology Neuroblastoma Group (HR-NBL1/SIOPEN) was performed at diagnosis and after induction therapy. High levels of TH, PHOX2B, or DCX mRNA in PB or BM at diagnosis strongly predicted for worse event-free survival (EFS) and overall survival (OS) in a cohort of 290 children. After induction therapy, high levels of these mRNAs predicted worse EFS and OS in BM but not in PB. Combinations of mRNAs in BM did not add to the predictive power of any single mRNA. However, in the original (n = 182) and validation (n = 137) PB cohorts, high TH (log10TH > 0.8) or high PHOX2B (log10PHOX2B > 0.28) identify 19% of children as ultrahigh risk, with 5-year EFS and OS rates of 0%; OS rate was 25% (95% CI, 16% to 36%) and EFS rate was 38% (95% CI, 28% to 49%) in the remaining children. The magnitude of reduction in mRNA level between diagnosis and postinduction therapy in BM or PB was not of additional predictive value. High levels of TH and PHOX2B mRNA in PB at diagnosis objectively identify children with ultrahigh-risk disease who may benefit from novel treatment approaches. The level of TH, PHOX2B, and DCX mRNA in BM and/or PB at diagnosis might contribute to an algorithm to improve stratification of children for treatment.

  9. Clinicodemographic aspect of resectable pancreatic cancer and prognostic factors for resectable cancer

    Directory of Open Access Journals (Sweden)

    Chiang Kun-Chun

    2012-05-01

    Full Text Available Abstract Background Pancreatic adenocarcinoma (PCA is one of the most lethal human malignancies, and radical surgery remains the cornerstone of treatment. After resection, the overall 5-year survival rate is only 10% to 29%. At the time of presentation, however, about 40% of patients generally have distant metastases and another 40% are usually diagnosed with locally advanced cancers. The remaining 20% of patients are indicated for surgery on the basis of the results of preoperative imaging studies; however, about half of these patients are found to be unsuitable for resection during surgical exploration. In the current study, we aimed to determine the clinicopathological characteristics that predict the resectability of PCA and to conduct a prognostic analysis of PCA after resection to identify favorable survival factors. Methods We retrospectively reviewed the medical files of 688 patients (422 men and 266 women who had undergone surgery for histopathologically proven PCA in the Department of Surgery at Chang Gung Memorial Hospital in Taiwan from 1981 to 2006. We compared the clinical characteristics of patients who underwent resection and patients who did not undergo resection in order to identify the predictive factors for successful resectability of PCA, and we conducted prognostic analysis for PCA after resection. Results A carbohydrate antigen 19–9 (CA 19–9 level of 37 U/ml or greater and a tumor size of 3 cm or more independently predicted resectability of PCA. In terms of survival after resection, PCA patients with better nutritional status (measured as having an albumin level greater than 3.5 g/dl, radical resection, early tumor stage and better-differentiated tumors were associated with favorable survival. Conclusions Besides traditional imaging studies, preoperative CA 19–9 levels and tumor size can also be used to determine the resectability of PCA. Better nutritional status, curative resection, early tumor stage and well

  10. Binimetinib inhibits MEK and is effective against neuroblastoma tumor cells with low NF1 expression

    International Nuclear Information System (INIS)

    Woodfield, Sarah E.; Zhang, Linna; Scorsone, Kathleen A.; Liu, Yin; Zage, Peter E.

    2016-01-01

    Novel therapies are needed for children with high-risk and relapsed neuroblastoma. We hypothesized that MAPK/ERK kinase (MEK) inhibition with the novel MEK1/2 inhibitor binimetinib would be effective in neuroblastoma preclinical models. Levels of total and phosphorylated MEK and extracellular signal-regulated kinase (ERK) were examined in primary neuroblastoma tumor samples and in neuroblastoma cell lines by Western blot. A panel of established neuroblastoma tumor cell lines was treated with increasing concentrations of binimetinib, and their viability was determined using MTT assays. Western blot analyses were performed to examine changes in total and phosphorylated MEK and ERK and to measure apoptosis in neuroblastoma tumor cells after binimetinib treatment. NF1 protein levels in neuroblastoma cell lines were determined using Western blot assays. Gene expression of NF1 and MEK1 was examined in relationship to neuroblastoma patient outcomes. Both primary neuroblastoma tumor samples and cell lines showed detectable levels of total and phosphorylated MEK and ERK. IC 50 values for cells sensitive to binimetinib ranged from 8 nM to 1.16 μM, while resistant cells did not demonstrate any significant reduction in cell viability with doses exceeding 15 μM. Sensitive cells showed higher endogenous expression of phosphorylated MEK and ERK. Gene expression of NF1, but not MEK1, correlated with patient outcomes in neuroblastoma, and NF1 protein expression also correlated with responses to binimetinib. Neuroblastoma tumor cells show a range of sensitivities to the novel MEK inhibitor binimetinib. In response to binimetinib, sensitive cells demonstrated complete loss of phosphorylated ERK, while resistant cells demonstrated either incomplete loss of ERK phosphorylation or minimal effects on MEK phosphorylation, suggesting alternative mechanisms of resistance. NF1 protein expression correlated with responses to binimetinib, supporting the use of NF1 as a biomarker to identify

  11. Imaging evaluation of infants with neuroblastoma detected by VMA screening spot test

    International Nuclear Information System (INIS)

    Fujioka, M.; Saiki, N.; Aihara, T.; Yamamoto, K.

    1988-01-01

    In the Saitama Prefecture in Japan, VMA (vanillyl manderic acid) screening spot test for detection of neuroblastoma has been performed in 173,046 infants in the years 1981-1986 and 15 infants were found to have neuroblastoma. Two infants had mediastinal tumors and the remainder, 13, had intraabdominal tumors. Only 7 infants had palpable masses. Although CT was documented to be the best imaging procedure to provide sufficient information for treatment, conventional radiographic examinations of the chest and abdomen, and abdominal ultrasonography were able, as initial imaging procedures, to detect reasonably small neuroblastomas in infants with a positive VMA screening test. (orig.)

  12. The therapeutic use of I-131 meta-iodobenzylguanidine (MIBG) in neuroblastoma

    International Nuclear Information System (INIS)

    Hartmann, O.; Lumbroso, J.D.; Lemerle, J.; Schlumberger, M.; Parmentier, C.; Ricard, M.; Aubert, B.; Coornaert, S.; Merlin, L.

    1988-01-01

    Despite the use of intensified conventional chemotherapy the complete response rate of advanced neuroblastoma remains low. The use of high-dose chemo-radiotherapy followed by bone marrow transplantation (BMT) improved the duration of disease free survival but, even after these high-dose regimens the relapse rate remains high. Metaiodobenzylguanidine (MIBG) labelled with I-131 or I-123 can be used for scintigraphic imaging of neuroblastoma. In order to evaluate the therapeutic role of I-131-MIBG in the treatment of neuroblastoma patients, a phase II study was performed in 12 patients. Results are presented in this paper

  13. Vitamin K3 analogs induce selective tumor cytotoxicity in neuroblastoma.

    Science.gov (United States)

    Kitano, Toru; Yoda, Hiroyuki; Tabata, Keiichi; Miura, Motofumi; Toriyama, Masaharu; Motohashi, Shigeyasu; Suzuki, Takashi

    2012-01-01

    We investigated the cytotoxicity of eight vitamin K3 (VK3) analogs against neuroblastoma cell lines (IMR-32, LA-N-1, NB-39, and SK-N-SH) and normal cell lines (human umbilical vein endothelial cells (HUVEC) and human dermal fibroblasts (HDF)) using a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. 2-[(2-Methoxy)ethylthio]-3-methyl-1,4-naphthoquinone (VK3-OCH(3)) showed especially potent cytotoxic activities against neuroblastoma cells compared with normal cells. In a Hoechst 33342 staining experiment, apoptotic morphologies characterized by cell shrinkage, nuclear condensation, and nuclear fragmentation were observed in IMR-32 and LA-N-1 cells after 48 h of treatment with 10(-5) M of VK3-OCH(3). To clarify the molecular mechanisms of apoptosis induced by VK3-OCH(3), we examined the expression of apoptosis related proteins using a Proteome Profiler Array and western blotting. Heme oxygenase (HO)-1 was remarkably increased by VK3-OCH(3) compared with the control (173% in IMR-32 and 170% in LA-N-1 at 24 h). Moreover, caveolin-1 was induced by VK3-OCH(3) at 48 h. In addition, VK3-OCH(3) arrested the cell cycle at the G2/M phase in IMR-32 cells. These results suggest that VK3-OCH(3) exhibited a selective antitumor activity via HO-1-related mechanisms.

  14. Treatment of neuroblastoma with metaiodobenzylguanidine: results and side effects

    International Nuclear Information System (INIS)

    Treuner, J.; Klingebiel, T.; Bruchelt, G.; Feine, U.; Niethammer, D.

    1987-01-01

    Between April 1984 and December 1985 we treated ten children suffering from neuroblastoma in a total of 25 metaiodobenzylguanidine (MIBG) courses. Five had had a relapse of neuroblastoma stage III or IV, three had never achieved a remission in spite of intensive chemotherapy, and two were treated with an unstable remission. The children were each administered from 1 to 5 courses with a dosage per course of between 1295 and 9065 MBq. The sum of the single doses during the whole course of therapy ranged between 3145 and 21,904 MBq per child. Five of five children suffering from bone pain and fever became free of complaints during the first three treatment days. Six of eight children with manifest tumor at onset of therapy responded well to the treatment: response extended from transitory decrease in elevated catecholamine levels in serum and urine to complete disappearance of large abdominal tumor masses. We also observed a decrease in bone marrow involvement and a stabilization of osteolytic lesions. Seven of these eight children died in spite of a good response from 55 to 350 days after the first MIBG treatment course. The only side effect we witnessed was a reversible bone marrow depression. In three children we combined the MIBG therapy with bone marrow transplantation

  15. ARID1B alterations identify aggressive tumors in neuroblastoma.

    Science.gov (United States)

    Lee, Soo Hyun; Kim, Jung-Sun; Zheng, Siyuan; Huse, Jason T; Bae, Joon Seol; Lee, Ji Won; Yoo, Keon Hee; Koo, Hong Hoe; Kyung, Sungkyu; Park, Woong-Yang; Sung, Ki W

    2017-07-11

    Targeted panel sequencing was performed to determine molecular targets and biomarkers in 72 children with neuroblastoma. Frequent genetic alterations were detected in ALK (16.7%), BRCA1 (13.9%), ATM (12.5%), and PTCH1 (11.1%) in an 83-gene panel. Molecular targets for targeted therapy were identified in 16 of 72 patients (22.2%). Two-thirds of ALK mutations were known to increase sensitivity to ALK inhibitors. Sequence alterations in ARID1B were identified in 5 of 72 patients (6.9%). Four of five ARID1B alterations were detected in tumors of high-risk patients. Two of five patients with ARID1B alterations died of disease progression. Relapse-free survival was lower in patients with ARID1B alterations than in those without (p = 0.01). In analysis confined to high-risk patients, 3-year overall survival was lower in patients with an ARID1B alteration (33.3 ± 27.2%) or MYCN amplification (30.0 ± 23.9%) than in those with neither ARID1B alteration nor MYCN amplification (90.5 ± 6.4%, p = 0.05). These results provide possibilities for targeted therapy and a new biomarker identifying a subgroup of neuroblastoma patients with poor prognosis.

  16. A 6-gene signature identifies four molecular subgroups of neuroblastoma

    Science.gov (United States)

    2011-01-01

    Background There are currently three postulated genomic subtypes of the childhood tumour neuroblastoma (NB); Type 1, Type 2A, and Type 2B. The most aggressive forms of NB are characterized by amplification of the oncogene MYCN (MNA) and low expression of the favourable marker NTRK1. Recently, mutations or high expression of the familial predisposition gene Anaplastic Lymphoma Kinase (ALK) was associated to unfavourable biology of sporadic NB. Also, various other genes have been linked to NB pathogenesis. Results The present study explores subgroup discrimination by gene expression profiling using three published microarray studies on NB (47 samples). Four distinct clusters were identified by Principal Components Analysis (PCA) in two separate data sets, which could be verified by an unsupervised hierarchical clustering in a third independent data set (101 NB samples) using a set of 74 discriminative genes. The expression signature of six NB-associated genes ALK, BIRC5, CCND1, MYCN, NTRK1, and PHOX2B, significantly discriminated the four clusters (p INSS stage 4 and/or dead of disease, p < 0.05, Fisher's exact test). Conclusions Based on expression profiling we have identified four molecular subgroups of neuroblastoma, which can be distinguished by a 6-gene signature. The fourth subgroup has not been described elsewhere, and efforts are currently made to further investigate this group's specific characteristics. PMID:21492432

  17. A 6-gene signature identifies four molecular subgroups of neuroblastoma

    Directory of Open Access Journals (Sweden)

    Kogner Per

    2011-04-01

    Full Text Available Abstract Background There are currently three postulated genomic subtypes of the childhood tumour neuroblastoma (NB; Type 1, Type 2A, and Type 2B. The most aggressive forms of NB are characterized by amplification of the oncogene MYCN (MNA and low expression of the favourable marker NTRK1. Recently, mutations or high expression of the familial predisposition gene Anaplastic Lymphoma Kinase (ALK was associated to unfavourable biology of sporadic NB. Also, various other genes have been linked to NB pathogenesis. Results The present study explores subgroup discrimination by gene expression profiling using three published microarray studies on NB (47 samples. Four distinct clusters were identified by Principal Components Analysis (PCA in two separate data sets, which could be verified by an unsupervised hierarchical clustering in a third independent data set (101 NB samples using a set of 74 discriminative genes. The expression signature of six NB-associated genes ALK, BIRC5, CCND1, MYCN, NTRK1, and PHOX2B, significantly discriminated the four clusters (p ALK, BIRC5, and PHOX2B, and was significantly associated with higher tumour stage, poor outcome and poor survival compared to the Type 1-corresponding favourable group (INSS stage 4 and/or dead of disease, p Conclusions Based on expression profiling we have identified four molecular subgroups of neuroblastoma, which can be distinguished by a 6-gene signature. The fourth subgroup has not been described elsewhere, and efforts are currently made to further investigate this group's specific characteristics.

  18. Anti-Neuroblastoma Properties of a Recombinant Sunflower Lectin

    Directory of Open Access Journals (Sweden)

    Marcela Pinedo

    2017-01-01

    Full Text Available According to their sugar recognition specificity, plant lectins are proposed as bioactive proteins with potential in cancer treatment and diagnosis. Helja is a mannose-specific jacalin-like lectin from sunflower which was shown to inhibit the growth of certain fungi. Here, we report its recombinant expression in a prokaryotic system and its activity in neurobalstoma cells. Helja coding sequence was fused to the pET-32 EK/LIC, the enterokinase/Ligation-independent cloning vector and a 35 kDa protein was obtained in Escherichia coli representing Helja coupled to thioredoxin (Trx. The identity of this protein was verified using anti-Helja antibodies. This chimera, named Trx-rHelja, was enriched in the soluble bacterial extracts and was purified using Ni+2-Sepharose and d-mannose-agarose chromatography. Trx-rHelja and the enterokinase-released recombinant Helja (rHelja both displayed toxicity on human SH-SY5Y neuroblastomas. rHelja decreased the viability of these tumor cells by 75% according to the tetrazolium reduction assay, and microscopic analyses revealed that the cell morphology was disturbed. Thus, the stellate cells of the monolayer became spheroids and were isolated. Our results indicate that rHelja is a promising tool for the development of diagnostic or therapeutic methods for neuroblastoma cells, the most common solid tumors in childhood.

  19. Identification of nuclear τ isoforms in human neuroblastoma cells

    International Nuclear Information System (INIS)

    Loomis, P.A.; Howard, T.H.; Castleberry, R.P.; Binder, L.I.

    1990-01-01

    The τ proteins have been reported only in association with microtubules and with ribosomes in situ, in the normal central nervous system. In addition, τ has been shown to be an integral component of paired helical filaments, the principal constituent of the neurofibrillary tangles found in brains of patients with Alzheimer's disease and of most aged individuals with Down syndrome (trisomy 21). The authors report here the localization of the well-characterized Tau-1 monoclonal antibody to the nucleolar organizer regions of the acrocentric chromosomes and to their interphase counterpart, the fibrillar component of the nucleolus, in human neuroblastoma cells. Similar localization to the nucleolar organizer regions was also observed in other human cell lines and in one monkey kidney cell line but was not seen in non-primate species. Immunochemically, they further demonstrated the existence of the entire τ molecule in the isolated nuclei of neuroblastoma cells. Nuclear τ proteins, like the τ proteins of the paired helical filaments, cannot be extracted in standard SDS-containing electrophoresis sample buffer but require pretreatment with formic acid prior to immunoblot analysis. This work indicates that τ may function in processes not directly associated with microtubules and that highly insoluble complexes of τ may also play a role in normal cellular physiology

  20. Risk factors for scoliosis in children with neuroblastoma

    International Nuclear Information System (INIS)

    Paulino, Arnold C.; Fowler, B. Zach

    2005-01-01

    Purpose: To determine the risk factors for scoliosis in children treated for neuroblastoma. Methods and materials: From 1957 to 1997, 58 children with neuroblastoma were treated at one institution and have survived a minimum of 5 years. There were 35 boys and 23 girls with a median age of 6 months (range, 2 weeks to 15 years) at initial diagnosis. Primary site was located in the adrenal gland in 25 (43.1%), abdominal/nonadrenal in 16 (27.6%), thoracic in 12 (20.7%), cervical in 3 (5.3%), and pelvic region in 2 (3.5%). The International Neuroblastoma Staging System (INSS) stage was Stage 1 in 10 (17.2%), Stage 2A in 7 (12.1%), Stage 2B in 5 (8.6%), Stage 3 in 22 (37.9%), Stage 4 in 4 (6.9%), and Stage 4S in 10 (17.2%). Thirty-three (56.9%) received chemotherapy whereas 5 (8.6%) had a laminectomy as part of the surgical procedure. Twenty-seven (46.6%) received radiotherapy (RT). Beam energy was 1.25 MV in 11 (41%), 250 kV in 10 (37%), 4 MV in 4 (15%), and 6-MV photons in 1 patient. One patient received 300 cGy in 1 fraction total skin RT using 6-MeV electrons. For the remaining patients, fraction size was 100 cGy in 6 (22%), 150-180 cGy in 11 (41%), 200 cGy in 4 (15%), and 250-300 cGy in 3. Three patients had total body irradiation at 333 cGy for 3 fractions. For all children who received RT, median total dose was 2000 cGy (range, 300-3900 cGy). Patients who were treated with RT had plain films of the irradiated area every 1 to 2 years until at least the age of puberty. Median follow-up was 10 years (range, 5-46 years). Results: The overall 5-, 10-, and 15-year scoliosis-free rates were 87.6%, 79.0%, and 76.0% respectively. Twelve (21%) developed scoliosis at a median time of 51 months (range, 8-137 months). The degree of scoliosis was mild (≤20 deg ) in 8 (67%). Four had scoliosis ranging from 30 deg to 66 deg ; 3 of these patients required surgical intervention, whereas 1 had an underlying Duchenne muscular dystrophy which manifested itself 8 years after

  1. Contemporary Management of Localized Resectable Pancreatic Cancer.

    Science.gov (United States)

    Kommalapati, Anuhya; Tella, Sri Harsha; Goyal, Gaurav; Ma, Wen Wee; Mahipal, Amit

    2018-01-20

    Pancreatic cancer is the third most common cause of cancer deaths in the United States. Surgical resection with negative margins still constitutes the cornerstone of potentially curative therapy, but is possible only in 15-20% of patients at the time of initial diagnosis. Accumulating evidence suggests that the neoadjuvant approach may improve R0 resection rate in localized resectable and borderline resectable diseases, and potentially downstage locally advanced disease to achieve surgical resection, though the impact on survival is to be determined. Despite advancements in the last decade in developing effective combinational chemo-radio therapeutic options, preoperative treatment strategies, and better peri-operative care, pancreatic cancer continues to carry a dismal prognosis in the majority. Prodigious efforts are currently being made in optimizing the neoadjuvant therapy with a better toxicity profile, developing novel agents, imaging techniques, and identification of biomarkers for the disease. Advancement in our understanding of the tumor microenvironment and molecular pathology is urgently needed to facilitate the development of novel targeted and immunotherapies for this setting. In this review, we detail the current literature on contemporary management of resectable, borderline resectable and locally advanced pancreatic cancer with a focus on future directions in the field.

  2. Augmented reality in a tumor resection model.

    Science.gov (United States)

    Chauvet, Pauline; Collins, Toby; Debize, Clement; Novais-Gameiro, Lorraine; Pereira, Bruno; Bartoli, Adrien; Canis, Michel; Bourdel, Nicolas

    2018-03-01

    Augmented Reality (AR) guidance is a technology that allows a surgeon to see sub-surface structures, by overlaying pre-operative imaging data on a live laparoscopic video. Our objectives were to evaluate a state-of-the-art AR guidance system in a tumor surgical resection model, comparing the accuracy of the resection with and without the system. Our system has three phases. Phase 1: using the MRI images, the kidney's and pseudotumor's surfaces are segmented to construct a 3D model. Phase 2: the intra-operative 3D model of the kidney is computed. Phase 3: the pre-operative and intra-operative models are registered, and the laparoscopic view is augmented with the pre-operative data. We performed a prospective experimental study on ex vivo porcine kidneys. Alginate was injected into the parenchyma to create pseudotumors measuring 4-10 mm. The kidneys were then analyzed by MRI. Next, the kidneys were placed into pelvictrainers, and the pseudotumors were laparoscopically resected. The AR guidance system allows the surgeon to see tumors and margins using classical laparoscopic instruments, and a classical screen. The resection margins were measured microscopically to evaluate the accuracy of resection. Ninety tumors were segmented: 28 were used to optimize the AR software, and 62 were used to randomly compare surgical resection: 29 tumors were resected using AR and 33 without AR. The analysis of our pathological results showed 4 failures (tumor with positive margins) (13.8%) in the AR group, and 10 (30.3%) in the Non-AR group. There was no complete miss in the AR group, while there were 4 complete misses in the non-AR group. In total, 14 (42.4%) tumors were completely missed or had a positive margin in the non-AR group. Our AR system enhances the accuracy of surgical resection, particularly for small tumors. Crucial information such as resection margins and vascularization could also be displayed.

  3. Robotic liver surgery: results for 70 resections.

    Science.gov (United States)

    Giulianotti, Pier Cristoforo; Coratti, Andrea; Sbrana, Fabio; Addeo, Pietro; Bianco, Francesco Maria; Buchs, Nicolas Christian; Annechiarico, Mario; Benedetti, Enrico

    2011-01-01

    Robotic surgery is gaining popularity for digestive surgery; however, its use for liver surgery is reported scarcely. This article reviews a surgeon's experience with the use of robotic surgery for liver resections. From March 2002 to March 2009, 70 robotic liver resections were performed at 2 different centers by a single surgeon. The surgical procedure and postoperative outcome data were reviewed retrospectively. Malignant tumors were indications for resections in 42 (60%) patients, whereas benign tumors were indications in 28 (40%) patients. The median age was 60 years (range, 21-84) and 57% of patients were female. Major liver resections (≥ 3 liver segments) were performed in 27 (38.5%) patients. There were 4 conversions to open surgery (5.7%). The median operative time for a major resection was 313 min (range, 220-480) and 198 min (range, 90-459) for minor resection. The median blood loss was 150 mL (range, 20-1,800) for minor resection and 300 mL (range, 100-2,000) for major resection. The mortality rate was 0%, and the overall rate of complications was 21%. Major morbidity occurred in 4 patients in the major hepatectomies group (14.8%) and in 4 patients in the minor hepatectomies group (9.3%). All complications were managed conservatively and none required reoperation. This preliminary experience shows that robotic surgery can be used safely for liver resections with a limited conversion rate, blood loss, and postoperative morbidity. Robotics offers a new technical option for minimally invasive liver surgery. Copyright © 2011 Mosby, Inc. All rights reserved.

  4. Water Leak Localisation and Recovery in Tore Supra

    International Nuclear Information System (INIS)

    Martinez, A.; Samaille, F.; Chantant, M.; Hatchressian, J.-C.

    2006-01-01

    For almost 20 years, Tore Supra (TS) Tokamak uses water as a coolant for its plasma facing and in-vessels components. It can be considered as ITER relevant on this particular aspect. During plasma operation in TS, the water inlet temperature and outlet pressure are 120 o C and 2.4 MPa respectively, while baking is performed at 200 o C and 2 Mpa. It happened, that unexpected localized power deposits damaged in-vessels components leading to more or less large water leaks. In order to protect the vacuum vessel from over-pressurisation in case of large water leaks and to avoid the release of eventual activated materials, a pressure suppression system, composed of two rupture disks and a relief pipe header, has been designed. In the event of smaller leaks, the issue for Tore Supra operations is to apply methods capable of detecting and localising leaking water cooling circuits inside the vacuum vessel within an acceptable time. For this purpose, drainage and drying systems have been designed and manufactured to evacuate completely the water in the components and vacuum vessel, facilitating, in that way, leak testing procedure of the components. A new system allows the localization of the leaky circuit remotely by using the cooling loops monitoring system. The sub-circuits can be selected, isolated and de pressurized by the operator. Simultaneously the vacuum is monitored in the vessel and analyzed with a mass spectrometer. The water resulting from the steam condensation in the cold parts of the vacuum vessel is pumped by a new specific vacuum system in the lower parts of the machine and stored in tanks to avoid dissipation of activated products in the environment. Filters are implemented on the outlets lines of the pumps. The in-vessels components fed by the upper part of the cooling loop are connected in parallel and the water inlets and outlets are located on top of the machine, so some difficulties were encountered to drain-off completely this components. Presently

  5. Plato: A localised orbital based density functional theory code

    Science.gov (United States)

    Kenny, S. D.; Horsfield, A. P.

    2009-12-01

    The Plato package allows both orthogonal and non-orthogonal tight-binding as well as density functional theory (DFT) calculations to be performed within a single framework. The package also provides extensive tools for analysing the results of simulations as well as a number of tools for creating input files. The code is based upon the ideas first discussed in Sankey and Niklewski (1989) [1] with extensions to allow high-quality DFT calculations to be performed. DFT calculations can utilise either the local density approximation or the generalised gradient approximation. Basis sets from minimal basis through to ones containing multiple radial functions per angular momenta and polarisation functions can be used. Illustrations of how the package has been employed are given along with instructions for its utilisation. Program summaryProgram title: Plato Catalogue identifier: AEFC_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AEFC_v1_0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: Standard CPC licence, http://cpc.cs.qub.ac.uk/licence/licence.html No. of lines in distributed program, including test data, etc.: 219 974 No. of bytes in distributed program, including test data, etc.: 1 821 493 Distribution format: tar.gz Programming language: C/MPI and PERL Computer: Apple Macintosh, PC, Unix machines Operating system: Unix, Linux and Mac OS X Has the code been vectorised or parallelised?: Yes, up to 256 processors tested RAM: Up to 2 Gbytes per processor Classification: 7.3 External routines: LAPACK, BLAS and optionally ScaLAPACK, BLACS, PBLAS, FFTW Nature of problem: Density functional theory study of electronic structure and total energies of molecules, crystals and surfaces. Solution method: Localised orbital based density functional theory. Restrictions: Tight-binding and density functional theory only, no exact exchange. Unusual features: Both atom centred and uniform meshes available

  6. Endoscopic full-thickness resection: Current status.

    Science.gov (United States)

    Schmidt, Arthur; Meier, Benjamin; Caca, Karel

    2015-08-21

    Conventional endoscopic resection techniques such as endoscopic mucosal resection or endoscopic submucosal dissection are powerful tools for treatment of gastrointestinal neoplasms. However, those techniques are restricted to superficial layers of the gastrointestinal wall. Endoscopic full-thickness resection (EFTR) is an evolving technique, which is just about to enter clinical routine. It is not only a powerful tool for diagnostic tissue acquisition but also has the potential to spare surgical therapy in selected patients. This review will give an overview about current EFTR techniques and devices.

  7. CT on diagnosis and differential diagnosis of adrenal neuroblastoma from nephroblastoma in children

    International Nuclear Information System (INIS)

    Han Jingtian; Shen Guoqiang; Yang Huayuan

    2000-01-01

    Objective: To evaluate the effect of CT on diagnosis and differential diagnosis of children's adrenal neuroblastoma from nephroblastoma. Materials and Method: To analyse the CT manifestations on 36 cases of adrenal neuroblastoma and 32 cases of nephroblastoma both confirmed by postoperative pathologic diagnosis. Results: The adrenal neuroblastoma is a kind of extrarenal tumor, so the kidney kept its original form and showed some compressive features. The incidence of tumor calcification appeared mostly in rough and speckle-piece form was high. While the nephroblastoma is a renal tumor. The surrounding renal parenchyma showed a specific 'new-moon shape' intensification. Conclusion: CT is one of the most valuable and effective means of examination to diagnose adrenal neuroblastoma and differentiate it from nephroblastoma. It can provide important information for making correct diagnosis, planning proper therapy and assessing prognosis

  8. Gene therapy as a potential tool for treating neuroblastoma-a focused review.

    Science.gov (United States)

    Kumar, M D; Dravid, A; Kumar, A; Sen, D

    2016-05-01

    Neuroblastoma, a solid tumor caused by rapid division of undifferentiated neuroblasts, is the most common childhood malignancy affecting children aged genes is restored to normalcy. Gene therapy is a powerful tool with the potential to inhibit the deleterious effects of oncogenes by inserting corrected/normal genes into the genome. Both viral and non-viral vector-based gene therapies have been developed and adopted to deliver the target genes into neuroblastoma cells. These attempts have given hope to bringing in a new regime of treatment against neuroblastoma. A few gene-therapy-based treatment strategies have been tested in limited clinical trials yielding some positive results. This mini review is an attempt to provide an overview of the available options of gene therapy to treat neuroblastoma.

  9. [The reaction of the neuroblastoma cells in the culture on the influence of tretionine and neurotoxine].

    Science.gov (United States)

    Magakian, Iu A; Karalian, Z A; Karalova, E M; Abroian, L O; Akopian, L A; Avetisian, A C; Semerdzhian, Z B

    2011-01-01

    Effect of the tretionine (retinoid) and aluminum chloride (neurotoxin) on the growth and differentiation of neuroblastoma cells in culture after their introduction into the medium separately and in combination was studied. The introduction of these substances creates a new information field in the medium, which becomes apparent by the reactions of neuroblastoma found on the populational and cellular levels of its organization. The presence of tretionine stimulates proliferation and induces differentiation of the cells into astrocytes. Aluminum chloride inhibits cell proliferation and enhances the process of their destruction in the monolayer. The variety of the reactions of neuroblastoma cells to the presence of these substances in the medium indicates the existence and functioning of a mechanism that selects from the information introduced only the portion which may contribute to adaptation of neuroblastoma cells to the changed culture conditions.

  10. Genomewide analysis of gene expression associated with Tcof1 in mouse neuroblastoma

    International Nuclear Information System (INIS)

    Mogass, Michael; York, Timothy P.; Li, Lin; Rujirabanjerd, Sinitdhorn; Shiang, Rita

    2004-01-01

    Mutations in the Treacher Collins syndrome gene, TCOF1, cause a disorder of craniofacial development. We manipulated the levels of Tcof1 and its protein treacle in a murine neuroblastoma cell line to identify downstream changes in gene expression using a microarray platform. We identified a set of genes that have similar expression with Tcof1 as well as a set of genes that are negatively correlated with Tcof1 expression. We also showed that the level of Tcof1 and treacle expression is downregulated during differentiation of neuroblastoma cells into neuronal cells. Inhibition of Tcof1 expression by siRNA induced morphological changes in neuroblastoma cells that mimic differentiation. Thus, expression of Tcof1 and treacle synthesis play an important role in the proliferation of neuroblastoma cells and we have identified genes that may be important in this pathway

  11. 131I-metaiodobenzylguanidine in the treatment of neuroblastoma at diagnosis

    International Nuclear Information System (INIS)

    Mastrangelo, R.; Troncone, L.; Lasorella, A.; Riccardi, R.; Montemaggi, P.; Rufini, V.

    1989-01-01

    Radioactive metaiodobenzylguanidine ( 131 I-MIBG) is taken up specifically by neuroblastoma cells and appears to represent a new treatment modality in patients with advanced neuroblastoma. Taking into account the fact that all patients so far treated were heavily pretreated and resistant to chemotherapy, the results obtained appear encouraging. In order to explore further the potential role of this new drug in untreated patients, we treated with 131 I-MIBG a child with stage III neuroblastoma at diagnosis. We observed the complete disappearance of a large abdominal tumor mass after a relatively low dosage of 131 I-MIBG, with minimal hematologic toxicity. No further treatment was given and, at present, the patient is alive with no evidence of disease 18 months from diagnosis. This child represents, to our knowledge, the only case of neuroblastoma thus far treated at diagnosis and the excellent response obtained suggests the need for further investigations of this therapy in untreated patients

  12. LMO1 Synergizes with MYCN to Promote Neuroblastoma Initiation and Metastasis.

    Science.gov (United States)

    Zhu, Shizhen; Zhang, Xiaoling; Weichert-Leahey, Nina; Dong, Zhiwei; Zhang, Cheng; Lopez, Gonzalo; Tao, Ting; He, Shuning; Wood, Andrew C; Oldridge, Derek; Ung, Choong Yong; van Ree, Janine H; Khan, Amish; Salazar, Brittany M; Lummertz da Rocha, Edroaldo; Zimmerman, Mark W; Guo, Feng; Cao, Hong; Hou, Xiaonan; Weroha, S John; Perez-Atayde, Antonio R; Neuberg, Donna S; Meves, Alexander; McNiven, Mark A; van Deursen, Jan M; Li, Hu; Maris, John M; Look, A Thomas

    2017-09-11

    A genome-wide association study identified LMO1, which encodes an LIM-domain-only transcriptional cofactor, as a neuroblastoma susceptibility gene that functions as an oncogene in high-risk neuroblastoma. Here we show that dβh promoter-mediated expression of LMO1 in zebrafish synergizes with MYCN to increase the proliferation of hyperplastic sympathoadrenal precursor cells, leading to a reduced latency and increased penetrance of neuroblastomagenesis. The transgenic expression of LMO1 also promoted hematogenous dissemination and distant metastasis, which was linked to neuroblastoma cell invasion and migration, and elevated expression levels of genes affecting tumor cell-extracellular matrix interaction, including loxl3, itga2b, itga3, and itga5. Our results provide in vivo validation of LMO1 as an important oncogene that promotes neuroblastoma initiation, progression, and widespread metastatic dissemination. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Iodine-131 MIBG scintigraphy of the extremities in metastatic pheochromocytoma and neuroblastoma

    International Nuclear Information System (INIS)

    Shulkin, B.L.; Shen, S.W.; Sisson, J.C.; Shapiro, B.

    1987-01-01

    Iodine-131 MIBG scintigraphy may be used to determine the presence or absence of metastases to the appendicular skeleton in malignant pheochromocytoma and neuroblastoma. Normal bones show no uptake of [ 131 I]MIBG and the joints are seen as photon-deficient areas surrounded by background muscle activity. Discrete concentrations of radioactivity in bone are often seen in patients with malignant pheochromocytoma and neuroblastoma. Bone marrow involvement in neuroblastoma may be indicated by diffuse uptake of [ 131 I]MIBG or focal accumulation at the metaphyses. Uncommonly, bone involvement may not be displayed by the [ 131 I]MIBG images. Since conventional bone scanning agents may also fail to detect these tumors, skeletal scintigraphy with both [ 131 I]MIBG and [/sup 99m/Tc]MDP is necessary to reliably stage malignant pheochromocytoma and neuroblastoma

  14. Biokinetic and therapeutic use of 131I-MIBG in nude mice hosting human neuroblastoma xenografts

    International Nuclear Information System (INIS)

    Laubenbacher, C.; Kriegel, H.; Moellenstaedt, S.; Senekowitsch, R.; Technische Univ. Muenchen

    1988-01-01

    The biological halflife of 131 I-MIBG in nude mice with xenotransplanted human neuroblastoma derived from the SK-N-SH cell line comes to 6 h. The adrenal gland and the neuroblastoma show the highest uptake of MIBG. Based on these datas it could be calculated that 185 MBq would be necessary to get 60 Gy radiation absorbed dose in the tumor. 15-20 days after injection of this activity the tumors could no longer be palpated and they remained missing over the whole observation period. 92.5 MBq weren't enough getting a stable remission. Eleven days p.i. neuroblastoma started growing again. For the first time it could be shown that only high activity of 131 I-MIBG is able to restrain neuroblastoma totally. (orig.)

  15. Identification of BIRC6 as a novel intervention target for neuroblastoma therapy

    Directory of Open Access Journals (Sweden)

    Lamers Fieke

    2012-07-01

    Full Text Available Abstract Background Neuroblastoma are pediatric tumors of the sympathetic nervous system with a poor prognosis. Apoptosis is often deregulated in cancer cells, but only a few defects in apoptotic routes have been identified in neuroblastoma. Methods Here we investigated genomic aberrations affecting genes of the intrinsic apoptotic pathway in neuroblastoma. We analyzed DNA profiling data (CGH and SNP arrays and mRNA expression data of 31 genes of the intrinsic apoptotic pathway in a dataset of 88 neuroblastoma tumors using the R2 bioinformatic platform (http://r2.amc.nl. BIRC6 was selected for further analysis as a tumor driving gene. Knockdown experiments were performed using BIRC6 lentiviral shRNA and phenotype responses were analyzed by Western blot and MTT-assays. In addition, DIABLO levels and interactions were investigated with immunofluorescence and co-immunoprecipitation. Results We observed frequent gain of the BIRC6 gene on chromosome 2, which resulted in increased mRNA expression. BIRC6 is an inhibitor of apoptosis protein (IAP, that can bind and degrade the cytoplasmic fraction of the pro-apoptotic protein DIABLO. DIABLO mRNA expression was exceptionally high in neuroblastoma but the protein was only detected in the mitochondria. Upon silencing of BIRC6 by shRNA, DIABLO protein levels increased and cells went into apoptosis. Co-immunoprecipitation confirmed direct interaction between DIABLO and BIRC6 in neuroblastoma cell lines. Conclusion Our findings indicate that BIRC6 may have a potential oncogenic role in neuroblastoma by inactivating cytoplasmic DIABLO. BIRC6 inhibition may therefore provide a means for therapeutic intervention in neuroblastoma.

  16. MicroRNA-34a is a potent tumor suppressor molecule in vivo in neuroblastoma.

    LENUS (Irish Health Repository)

    Tivnan, Amanda

    2011-01-01

    Neuroblastoma is a paediatric cancer which originates from precursor cells of the sympathetic nervous system and accounts for 15% of childhood cancer mortalities. With regards to the role of miRNAs in neuroblastoma, miR-34a, mapping to a chromosome 1p36 region that is commonly deleted, has been found to act as a tumor suppressor through targeting of numerous genes associated with cell proliferation and apoptosis.

  17. Introduction of in vitro transcribed ENO1 mRNA into neuroblastoma cells induces cell death

    International Nuclear Information System (INIS)

    Ejeskär, Katarina; Krona, Cecilia; Carén, Helena; Zaibak, Faten; Li, Lingli; Martinsson, Tommy; Ioannou, Panayiotis A

    2005-01-01

    Neuroblastoma is a solid tumour of childhood often with an unfavourable outcome. One common genetic feature in aggressive tumours is 1p-deletion. The α-enolase (ENO1) gene is located in chromosome region 1p36.2, within the common region of deletion in neuroblastoma. One alternative translated product of the ENO1 gene, known as MBP-1, acts as a negative regulator of the c-myc oncogene, making the ENO1 gene a candidate as a tumour suppressor gene. Methods used in this study are transfection of cDNA-vectors and in vitro transcribed mRNA, cell growth assay, TUNEL-assay, real-time RT-PCR (TaqMan) for expression studies, genomic sequencing and DHPLC for mutation detection. Here we demonstrate that transfection of ENO1 cDNA into 1p-deleted neuroblastoma cell lines causes' reduced number of viable cells over time compared to a negative control and that it induces apoptosis. Interestingly, a similar but much stronger dose-dependent reduction of cell growth was observed by transfection of in vitro transcribed ENO1 mRNA into neuroblastoma cells. These effects could also be shown in non-neuroblastoma cells (293-cells), indicating ENO1 to have general tumour suppressor activity. Expression of ENO1 is detectable in primary neuroblastomas of all different stages and no difference in the level of expression can be detected between 1p-deleted and 1p-intact tumour samples. Although small numbers (11 primary neuroblastomas), there is some evidence that Stage 4 tumours has a lower level of ENO1-mRNA than Stage 2 tumours (p = 0.01). However, mutation screening of 44 primary neuroblastomas of all different stages, failed to detect any mutations. Our studies indicate that ENO1 has tumour suppressor activity and that high level of ENO1 expression has growth inhibitory effects

  18. Intracellular fragment of NLRR3 (NLRR3-ICD) stimulates ATRA-dependent neuroblastoma differentiation

    International Nuclear Information System (INIS)

    Akter, Jesmin; Takatori, Atsushi; Islam, Md. Sazzadul; Nakazawa, Atsuko; Ozaki, Toshinori; Nagase, Hiroki; Nakagawara, Akira

    2014-01-01

    Highlights: • NLRR3 is a membrane protein highly expressed in favorable neuroblastoma. • NLRR3-ICD was produced through proteolytic processing by secretases. • NLRR3-ICD was induced to be translocated into cell nucleus following ATRA exposure. • NLRR3-ICD plays a pivotal role in ATRA-mediated neuroblastoma differentiation. - Abstract: We have previously identified neuronal leucine-rich repeat protein-3 (NLRR3) gene which is preferentially expressed in favorable human neuroblastomas as compared with unfavorable ones. In this study, we have found for the first time that NLRR3 is proteolytically processed by secretases and its intracellular domain (NLRR3-ICD) is then released to translocate into cell nucleus during ATRA-mediated neuroblastoma differentiation. According to our present observations, NLRR3-ICD was induced to accumulate in cell nucleus of neuroblastoma SH-SY5Y cells following ATRA treatment. Since the proteolytic cleavage of NLRR3 was blocked by α- or γ-secretase inhibitor, it is likely that NLRR3-ICD is produced through the secretase-mediated processing of NLRR3. Intriguingly, forced expression of NLRR3-ICD in neuroblastoma SK-N-BE cells significantly suppressed their proliferation as examined by a live-cell imaging system and colony formation assay. Similar results were also obtained in neuroblastoma TGW cells. Furthermore, overexpression of NLRR3-ICD stimulated ATRA-dependent neurite elongation in SK-N-BE cells. Together, our present results strongly suggest that NLRR3-ICD produced by the secretase-mediated proteolytic processing of NLRR3 plays a crucial role in ATRA-mediated neuronal differentiation, and provide a clue to develop a novel therapeutic strategy against aggressive neuroblastomas

  19. Identification of BIRC6 as a novel intervention target for neuroblastoma therapy

    International Nuclear Information System (INIS)

    Lamers, Fieke; Molenaar, Jan J; Schild, Linda; Koster, Jan; Speleman, Frank; Øra, Ingrid; Westerhout, Ellen M; Sluis, Peter van; Versteeg, Rogier; Caron, Huib N

    2012-01-01

    Neuroblastoma are pediatric tumors of the sympathetic nervous system with a poor prognosis. Apoptosis is often deregulated in cancer cells, but only a few defects in apoptotic routes have been identified in neuroblastoma. Here we investigated genomic aberrations affecting genes of the intrinsic apoptotic pathway in neuroblastoma. We analyzed DNA profiling data (CGH and SNP arrays) and mRNA expression data of 31 genes of the intrinsic apoptotic pathway in a dataset of 88 neuroblastoma tumors using the R2 bioinformatic platform. BIRC6 was selected for further analysis as a tumor driving gene. Knockdown experiments were performed using BIRC6 lentiviral shRNA and phenotype responses were analyzed by Western blot and MTT-assays. In addition, DIABLO levels and interactions were investigated with immunofluorescence and co-immunoprecipitation. We observed frequent gain of the BIRC6 gene on chromosome 2, which resulted in increased mRNA expression. BIRC6 is an inhibitor of apoptosis protein (IAP), that can bind and degrade the cytoplasmic fraction of the pro-apoptotic protein DIABLO. DIABLO mRNA expression was exceptionally high in neuroblastoma but the protein was only detected in the mitochondria. Upon silencing of BIRC6 by shRNA, DIABLO protein levels increased and cells went into apoptosis. Co-immunoprecipitation confirmed direct interaction between DIABLO and BIRC6 in neuroblastoma cell lines. Our findings indicate that BIRC6 may have a potential oncogenic role in neuroblastoma by inactivating cytoplasmic DIABLO. BIRC6 inhibition may therefore provide a means for therapeutic intervention in neuroblastoma

  20. Transcription factor activating protein 2 beta (TFAP2B) mediates noradrenergic neuronal differentiation in neuroblastoma.

    Science.gov (United States)

    Ikram, Fakhera; Ackermann, Sandra; Kahlert, Yvonne; Volland, Ruth; Roels, Frederik; Engesser, Anne; Hertwig, Falk; Kocak, Hayriye; Hero, Barbara; Dreidax, Daniel; Henrich, Kai-Oliver; Berthold, Frank; Nürnberg, Peter; Westermann, Frank; Fischer, Matthias

    2016-02-01

    Neuroblastoma is an embryonal pediatric tumor that originates from the developing sympathetic nervous system and shows a broad range of clinical behavior, ranging from fatal progression to differentiation into benign ganglioneuroma. In experimental neuroblastoma systems, retinoic acid (RA) effectively induces neuronal differentiation, and RA treatment has been therefore integrated in current therapies. However, the molecular mechanisms underlying differentiation are still poorly understood. We here investigated the role of transcription factor activating protein 2 beta (TFAP2B), a key factor in sympathetic nervous system development, in neuroblastoma pathogenesis and differentiation. Microarray analyses of primary neuroblastomas (n = 649) demonstrated that low TFAP2B expression was significantly associated with unfavorable prognostic markers as well as adverse patient outcome. We also found that low TFAP2B expression was strongly associated with CpG methylation of the TFAP2B locus in primary neuroblastomas (n = 105) and demethylation with 5-aza-2'-deoxycytidine resulted in induction of TFAP2B expression in vitro, suggesting that TFAP2B is silenced by genomic methylation. Tetracycline inducible re-expression of TFAP2B in IMR-32 and SH-EP neuroblastoma cells significantly impaired proliferation and cell cycle progression. In IMR-32 cells, TFAP2B induced neuronal differentiation, which was accompanied by up-regulation of the catecholamine biosynthesizing enzyme genes DBH and TH, and down-regulation of MYCN and REST, a master repressor of neuronal genes. By contrast, knockdown of TFAP2B by lentiviral transduction of shRNAs abrogated RA-induced neuronal differentiation of SH-SY5Y and SK-N-BE(2)c neuroblastoma cells almost completely. Taken together, our results suggest that TFAP2B is playing a vital role in retaining RA responsiveness and mediating noradrenergic neuronal differentiation in neuroblastoma. Copyright © 2015 Federation of European Biochemical Societies

  1. Intracellular fragment of NLRR3 (NLRR3-ICD) stimulates ATRA-dependent neuroblastoma differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Akter, Jesmin [Laboratory of Innovative Cancer Therapeutics, Chiba Cancer Center Research Institute, Chiba 260-8717 (Japan); Takatori, Atsushi, E-mail: atakatori@chiba-cc.jp [Laboratory of Cancer Genetics, Chiba Cancer Center Research Institute, Chiba 260-8717 (Japan); Islam, Md. Sazzadul [Laboratory of Innovative Cancer Therapeutics, Chiba Cancer Center Research Institute, Chiba 260-8717 (Japan); Nakazawa, Atsuko [Department of Pathology, National Center for Child Health and Development, Tokyo (Japan); Ozaki, Toshinori, E-mail: tozaki@chiba-cc.jp [Laboratory of DNA Damage Signaling, Chiba Cancer Center Research Institute, Chiba 260-8717 (Japan); Nagase, Hiroki [Laboratory of Cancer Genetics, Chiba Cancer Center Research Institute, Chiba 260-8717 (Japan); Nakagawara, Akira [Saga Medical Centre, 840-8571 (Japan)

    2014-10-10

    Highlights: • NLRR3 is a membrane protein highly expressed in favorable neuroblastoma. • NLRR3-ICD was produced through proteolytic processing by secretases. • NLRR3-ICD was induced to be translocated into cell nucleus following ATRA exposure. • NLRR3-ICD plays a pivotal role in ATRA-mediated neuroblastoma differentiation. - Abstract: We have previously identified neuronal leucine-rich repeat protein-3 (NLRR3) gene which is preferentially expressed in favorable human neuroblastomas as compared with unfavorable ones. In this study, we have found for the first time that NLRR3 is proteolytically processed by secretases and its intracellular domain (NLRR3-ICD) is then released to translocate into cell nucleus during ATRA-mediated neuroblastoma differentiation. According to our present observations, NLRR3-ICD was induced to accumulate in cell nucleus of neuroblastoma SH-SY5Y cells following ATRA treatment. Since the proteolytic cleavage of NLRR3 was blocked by α- or γ-secretase inhibitor, it is likely that NLRR3-ICD is produced through the secretase-mediated processing of NLRR3. Intriguingly, forced expression of NLRR3-ICD in neuroblastoma SK-N-BE cells significantly suppressed their proliferation as examined by a live-cell imaging system and colony formation assay. Similar results were also obtained in neuroblastoma TGW cells. Furthermore, overexpression of NLRR3-ICD stimulated ATRA-dependent neurite elongation in SK-N-BE cells. Together, our present results strongly suggest that NLRR3-ICD produced by the secretase-mediated proteolytic processing of NLRR3 plays a crucial role in ATRA-mediated neuronal differentiation, and provide a clue to develop a novel therapeutic strategy against aggressive neuroblastomas.

  2. Signaling pathways in PACAP regulation of VIP gene expression in human neuroblastoma cells

    DEFF Research Database (Denmark)

    Falktoft, B.; Georg, B.; Fahrenkrug, J.

    2009-01-01

    Ganglia expressing the neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) innervate vasoactive intestinal peptide (VIP) containing neurons suggesting a role of PACAP in regulating VIP expression. Human NB-1 neuroblastoma cells were applied to study PACAP regulated VIP gene...... in PACAP regulation of the FOS and VIP gene expressions suggest for the first time a role of FOS in PACAP-induced VIP gene expression in human NB-1 neuroblastoma cells. (C) 2009 Elsevier Ltd. All rights reserved Udgivelsesdato: 2009/10...

  3. Unusual fatty metamorphosis observed in diffuse liver metastases of stage 4S neuroblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Tazoe, Jun; Okuyama, Chio; Nishimura, Tsunehiko [Kyoto Prefectural University of Medicine, Department of Radiology, Graduate School of Medical Science, Kyoto City (Japan); Iehara, Tomoko; Hosoi, Hajime [Kyoto Prefectural University of Medicine, Department of Paediatrics, Graduate School of Medical Science, Kyoto City (Japan)

    2010-05-15

    We report a case of stage 4S neuroblastoma in which CT showed diffuse liver metastases containing a geographical fatty area in the periportal region. MRI showed this abnormality to correspond to an area with an unusual pattern of fatty change. {sup 123}I-metaiodobenzylguanidine (MIBG) scintigraphy demonstrated increased accumulation throughout the liver, except for the region showing fatty change. To the best of our knowledge, this is the first report of liver metastases from neuroblastoma with geographical fatty infiltration. (orig.)

  4. Unusual fatty metamorphosis observed in diffuse liver metastases of stage 4S neuroblastoma

    International Nuclear Information System (INIS)

    Tazoe, Jun; Okuyama, Chio; Nishimura, Tsunehiko; Iehara, Tomoko; Hosoi, Hajime

    2010-01-01

    We report a case of stage 4S neuroblastoma in which CT showed diffuse liver metastases containing a geographical fatty area in the periportal region. MRI showed this abnormality to correspond to an area with an unusual pattern of fatty change. 123 I-metaiodobenzylguanidine (MIBG) scintigraphy demonstrated increased accumulation throughout the liver, except for the region showing fatty change. To the best of our knowledge, this is the first report of liver metastases from neuroblastoma with geographical fatty infiltration. (orig.)

  5. Cdc25A localisation and shuttling: characterisation of sequences mediating nuclear export and import

    International Nuclear Information System (INIS)

    Kaellstroem, Helena; Lindqvist, Arne; Pospisil, Vitek; Lundgren, Andreas; Karlsson Rosenthal, Christina

    2005-01-01

    The Cdc25 phosphatases play crucial roles in cell cycle progression by removing inhibitory phosphates from tyrosine and threonine residues of cyclin-dependent kinases. Cdc25A is an important regulator of the G1/S transition but functions also in the mitotic phase of the human cell cycle. In this paper, we investigate the sub-cellular localisation of exogenously expressed Cdc25A. We show that YFP-Cdc25A is localised both in the nucleus and the cytoplasm of HeLa cells and untransformed fibroblasts. Cell fusion assays and fluorescence loss in photobleaching (FLIP) assays reveal that the localisation is dynamic and the protein shuttles between the nucleus and the cytoplasm. We demonstrate that nuclear export of Cdc25A is partly mediated by an N-terminal nuclear export sequence (NES), in a manner not sensitive to the Exportin 1-inhibitor leptomycin B. A nuclear localisation signal (NLS) is also characterised, mutation of which leads to cytoplasmic localisation of Cdc25A. Our results imply that the Cdc25A phosphatase may interact with substrates and regulators both in the nucleus and the cytoplasm

  6. A new range-free localisation in wireless sensor networks using support vector machine

    Science.gov (United States)

    Wang, Zengfeng; Zhang, Hao; Lu, Tingting; Sun, Yujuan; Liu, Xing

    2018-02-01

    Location information of sensor nodes is of vital importance for most applications in wireless sensor networks (WSNs). This paper proposes a new range-free localisation algorithm using support vector machine (SVM) and polar coordinate system (PCS), LSVM-PCS. In LSVM-PCS, two sets of classes are first constructed based on sensor nodes' polar coordinates. Using the boundaries of the defined classes, the operation region of WSN field is partitioned into a finite number of polar grids. Each sensor node can be localised into one of the polar grids by executing two localisation algorithms that are developed on the basis of SVM classification. The centre of the resident polar grid is then estimated as the location of the sensor node. In addition, a two-hop mass-spring optimisation (THMSO) is also proposed to further improve the localisation accuracy of LSVM-PCS. In THMSO, both neighbourhood information and non-neighbourhood information are used to refine the sensor node location. The results obtained verify that the proposed algorithm provides a significant improvement over existing localisation methods.

  7. Somatostatin receptor scintigraphy and intraoperative gamma probe detection in the localisation and treatment of pancreatic insulinoma

    International Nuclear Information System (INIS)

    Loh, Nelson K.; Macdonald, William B.; Dunne, Marina L.; Rao, Sudhakar

    2009-01-01

    Full text: Aims: We report a case of insulinoma that was successfully enucleated under radio-guidance after an initial unsuccessful laparotomy. This case highlights the utility of Somatostatin Receptor Scintigraphy (SRS) and gamma probe in the localisation and treatment of neuroendocrine tumours. Methods: The patient presented with recurrent hypoglycaemia. An abdominal CT scan identified a lesion in the uncinate process of the pancreas, however, laparotomy with use of intraoperative ultrasound failed to localise the lesion. SRS with SPECTICT was then requested by the surgical team with a view to radio-guided surgery. Results: SRS demonstrated an octreotide-avid tumour in the posterior uncinate process of the pancreas, and confirmed suitability for radio-guided surgery. At re-exploration, the surgeon was again unable to palpate the lesion or localise it with intraoperative ultrasound, however, the lesion was successfully detected and removed with the use of a gamma probe. A postoperative SRS confirmed complete excision and histopathology was diagnostic of insulinoma. Conclusion: This case highlights the utility of SRS in the intraoperative localisation and surgical excision of neuroendocrine tumours. The lesion was unable to be localised clinically or with intraoperative ultrasound but was successfully detected with scintigraphic techniques. The surgical team acknowledge that the use of a gamma probe enabled enucleation of the insulinoma, which obviated the need for an invasive Whipple's procedure.

  8. Treatment of non-resectable malignant iris tumours with custom designed plaque radiotherapy

    International Nuclear Information System (INIS)

    Shields, C.L.; Shields, J.A.; Potter, P. De; Singh, A.D.; Hernandez, C.; Brady, L.W.

    1995-01-01

    Background- Plaque radiotherapy is the most common method of managing posterior uveal melanoma but its use for iris melanoma and iris metastases has not yet been evaluated. Methods -Fourteen patients with non-resectable iris melanoma and four with iris metastasis were treated with plaque radiotherapy. The tumour response to treatment and the local side effects of the radioactive plaque were evaluated. Results -In the iris melanoma group over a mean follow up of 26 (range 6-75) months, the tumour regressed in 13 of the 14 patients (93%) and recurred as diffuse seeding in one patient (7%). Despite large doses of radiation given transcorneally, the cornea developed epitheliopathy, abraxion, and oedema in only one case each. The major radiation side effects were localised iris vasculopathy without glaucoma in two cases, posterior synechiae in five cases, and cataract in six cases. In the iris metastasis group, tumour regression was observed in all four patients (100%) and radiation side effects were not evident over the relatively short mean follow up period of 8 (range 4-9) months. All of the 14 patients with irradiated iris melanoma have remained systemically healthy without metastasis while three of the four patients with irradiated iris metastases have died of metastases from the primary neoplasm. Conclusion - Custom designed plaque radiotherapy appears to be an effective alternative method of controlling non-resectable diffuse iris melanoma and solitary iris metastasis and has relatively few side effects. (author)

  9. Optimizing Adjuvant Therapy for Resected Pancreatic Cancer

    Science.gov (United States)

    In this clinical trial, patients with resected pancreatic head cancer will be randomly assigned to receive either gemcitabine with or without erlotinib for 5 treatment cycles. Patients who do not experience disease progression or recurrence will then be r

  10. ACR Appropriateness Criteria on Resectable Rectal Cancer

    International Nuclear Information System (INIS)

    Suh, W. Warren; Blackstock, A. William; Herman, Joseph; Konski, Andre A.; Mohiuddin, Mohammed; Poggi, Matthew M.; Regine, William F.; Cosman, Bard C.; Saltz, Leonard; Johnstone, Peter A.S.

    2008-01-01

    The American College of Radiology (ACR) Appropriateness Criteria on Resectable Rectal Cancer was updated by the Expert Panel on Radiation Oncology-Rectal/Anal Cancer, based on a literature review completed in 2007

  11. Neuroblastoma cell lines contain pluripotent tumor initiating cells that are susceptible to a targeted oncolytic virus.

    Directory of Open Access Journals (Sweden)

    Yonatan Y Mahller

    Full Text Available Although disease remission can frequently be achieved for patients with neuroblastoma, relapse is common. The cancer stem cell theory suggests that rare tumorigenic cells, resistant to conventional therapy, are responsible for relapse. If true for neuroblastoma, improved cure rates may only be achieved via identification and therapeutic targeting of the neuroblastoma tumor initiating cell. Based on cues from normal stem cells, evidence for tumor populating progenitor cells has been found in a variety of cancers.Four of eight human neuroblastoma cell lines formed tumorspheres in neural stem cell media, and all contained some cells that expressed neurogenic stem cell markers including CD133, ABCG2, and nestin. Three lines tested could be induced into multi-lineage differentiation. LA-N-5 spheres were further studied and showed a verapamil-sensitive side population, relative resistance to doxorubicin, and CD133+ cells showed increased sphere formation and tumorigenicity. Oncolytic viruses, engineered to be clinically safe by genetic mutation, are emerging as next generation anticancer therapeutics. Because oncolytic viruses circumvent typical drug-resistance mechanisms, they may represent an effective therapy for chemotherapy-resistant tumor initiating cells. A Nestin-targeted oncolytic herpes simplex virus efficiently replicated within and killed neuroblastoma tumor initiating cells preventing their ability to form tumors in athymic nude mice.These results suggest that human neuroblastoma contains tumor initiating cells that may be effectively targeted by an oncolytic virus.

  12. Multiple mechanisms disrupt the let-7 microRNA family in neuroblastoma

    Science.gov (United States)

    Powers, John T; Tsanov, Kaloyan M; Pearson, Daniel S; Roels, Frederik; Spina, Catherine S; Ebright, Richard; Seligson, Marc; de Soysa, Yvanka; Cahan, Patrick; Theiβen, Jessica; Tu, Ho-Chou; Han, Areum; Kurek, Kyle C; LaPier, Grace S; Osborne, Jihan K; Ross, Samantha J; Cesana, Marcella; Collins, James J; Berthold, Frank; Daley, George Q

    2016-01-01

    Poor prognosis in neuroblastoma is associated with genetic amplification of MYCN. MYCN is itself a target of let-7, a tumor suppressor family of microRNAs implicated in numerous cancers. LIN28B, an inhibitor of let-7 biogenesis, is overexpressed in neuroblastoma and has been reported to regulate MYCN. However, here we show that LIN28B is dispensable in MYCN-amplified neuroblastoma cell lines, despite de-repression of let-7. We further demonstrate that MYCN mRNA levels in amplified disease are exceptionally high and sufficient to sponge let-7, which reconciles the dispensability of LIN28B. We found that genetic loss of let-7 is common in neuroblastoma, inversely associated with MYCN-amplification, and independently associated with poor outcomes, providing a rationale for chromosomal loss patterns in neuroblastoma. We propose that let-7 disruption by LIN28B, MYCN sponging, or genetic loss is a unifying mechanism of neuroblastoma pathogenesis with broad implications for cancer pathogenesis. PMID:27383785

  13. Dextran-Catechin: An anticancer chemically-modified natural compound targeting copper that attenuates neuroblastoma growth

    Science.gov (United States)

    Vittorio, Orazio; Brandl, Miriam; Cirillo, Giuseppe; Kimpton, Kathleen; Hinde, Elizabeth; Gaus, Katharina; Yee, Eugene; Kumar, Naresh; Duong, Hien; Fleming, Claudia; Haber, Michelle; Norris, Murray; Boyer, Cyrille; Kavallaris, Maria

    2016-01-01

    Neuroblastoma is frequently diagnosed at advanced stage disease and treatment includes high dose chemotherapy and surgery. Despite the use of aggressive therapy survival rates are poor and children that survive their disease experience long term side effects from their treatment, highlighting the need for effective and less toxic therapies. Catechin is a natural polyphenol with anti-cancer properties and limited side effects, however its mechanism of action is unknown. Here we report that Dextran-Catechin, a conjugated form of catechin that increases serum stability, is preferentially and markedly active against neuroblastoma cells having high levels of intracellular copper, without affecting non-malignant cells. Copper transporter 1 (CTR1) is the main transporter of copper in mammalian cells and it is upregulated in neuroblastoma. Functional studies showed that depletion of CTR1 expression reduced intracellular copper levels and led to a decrease in neuroblastoma cell sensitivity to Dextran-Catechin, implicating copper in the activity of this compound. Mechanistically, Dextran-Catechin was found to react with copper, inducing oxidative stress and decreasing glutathione levels, an intracellular antioxidant and regulator of copper homeostasis. In vivo, Dextran-Catechin significantly attenuated tumour growth in human xenograft and syngeneic models of neuroblastoma. Thus, Dextran-Catechin targets copper, inhibits tumour growth, and may be valuable in the treatment of aggressive neuroblastoma and other cancers dependent on copper for their growth. PMID:27374085

  14. Iodine-131 Metaiodobenzylguanidine Therapy for Neuroblastoma: Reports So Far and Future Perspective

    Directory of Open Access Journals (Sweden)

    Daiki Kayano

    2015-01-01

    Full Text Available Neuroblastoma, which derives from neural crest, is the most common extracranial solid cancer in childhood. The tumors express the norepinephrine (NE transporters on their cell membrane and take in metaiodobenzylguanidine (MIBG via a NE transporter. Since iodine-131 (I-131 MIBG therapy was firstly reported, many trails of MIBG therapy in patients with neuroblastoma were performed. Though monotherapy with a low dose of I-131 MIBG could achieve high-probability pain reduction, the objective response was poor. In contrast, more than 12 mCi/kg I-131 MIBG administrations with or without hematopoietic cell transplantation (HCT obtain relatively good responses in patients with refractory or relapsed neuroblastoma. The combination therapy with I-131 MIBG and other modalities such as nonmyeloablative chemotherapy and myeloablative chemotherapy with HCT improved the therapeutic response in patients with refractory or relapsed neuroblastoma. In addition, I-131 MIBG therapy incorporated in the induction therapy was proved to be feasible in patients with newly diagnosed neuroblastoma. To expand more the use of MIBG therapy for neuroblastoma, further studies will be needed especially in the use at an earlier stage from diagnosis, in the use with other radionuclide formations of MIBG, and in combined use with other therapeutic agents.

  15. Thoracic neuroblastoma: what is the best imaging modality for evaluating extent of disease?

    International Nuclear Information System (INIS)

    Slovis, T.L.; Meza, M.P.; Cushing, B.; Elkowitz, S.S.; Leonidas, J.C.; Festa, R.; Kogutt, M.S.; Fletcher, B.D.

    1997-01-01

    Thoracic neuroblastoma accounts for 15% of all cases of neuroblastoma. A minority of children with thoracic neuroblastoma will have dumbbell tumors, i.e., intraspinal extension, but only half these patients will have neurologic signs or symptoms. Hypothesis. MR imaging is the single best test to evaluate the extent of thoracic and spinal disease in thoracid neuroblastoma after the diagnosis of a mass is estbalished on plain film. A retrospective multi-institutional investigation over 7 years of all cases of thoracic neuroblastoma (n=26) imaged with CT and/or MR were reviewed for detection of the extent of disease. The chest film, nuclear bone scan, and other imaging modalities were also reviewed. The surgical and histologic correlation in each case, as well as the patients' staging and outcome, were tabulated. The chest radiography was 100% sensitive in suggesting the diagnosis. MR imaging was 100% sensitive in predicting enlarged lymph nodes, intraspinal extension, and chest wall involvement. CT was 88% sensitive for intraspinal extension but only 20% sensitive for lymph node enlargement. CT was 100% sensitive in detecting chest wall involvement. Direct comparison of CT and MR imaging in six cases revealed no difference in detection of enlarged lymph nodes or chest wall involvement. Neither test was able to detect remote disease, as noted by bone scan. The chest film is 100% sensitive in suggesting the diagnosis of thoracic neuroblastoma; MR imaging appears to be the single best test for detecting nodal involvement, intraspinal extension, and chest wall involvement. (orig.)

  16. RSRC1 and CPZ gene polymorphisms with neuroblastoma susceptibility in Chinese children.

    Science.gov (United States)

    Tang, Jue; Liu, Wei; Zhu, Jinhong; Zhang, Jiao; Wang, Feng-Hua; Liang, Jiang-Hua; Zeng, Jia-Hang; Wang, Hui; Xia, Huimin; He, Jing

    2018-07-01

    Two new neuroblastoma susceptibility loci at 3q25 (RSRC1 rs6441201 G > A) and 4p16 (CPZ rs3796725 T > C and rs3796727 A > G) were identified by a genome-wide association study (GWAS) involving Italians, African Americans and European Americans. In this case-control study with 393 neuroblastoma cases and 812 controls, we investigated the association between these three polymorphisms and neuroblastoma susceptibility in Chinese population. We found that participants harboring the RSRC1 rs6441201A allele were associated with an increased risk of neuroblastoma (AA vs. GG: adjusted OR = 1.55, 95% CI = 1.03-2.34, P = 0.036). No significant association between the CPZ polymorphisms (rs3796725 T > C and rs3796727A > G) and neuroblastoma susceptibility was observed. In conclusion, our results confirm that the RSRC1 rs6441201A allele is associated with neuroblastoma susceptibility in Chinese population. Copyright © 2018 Elsevier B.V. All rights reserved.

  17. Open resections for congenital lung malformations

    Directory of Open Access Journals (Sweden)

    Mullassery Dhanya

    2008-01-01

    Full Text Available Aim: Pediatric lung resection is a relatively uncommon procedure that is usually performed for congenital lesions. In recent years, thoracoscopic resection has become increasingly popular, particularly for small peripheral lesions. The aim of this study was to review our experience with traditional open lung resection in order to evaluate the existing "gold standard." Materials and Methods: We carried out a retrospective analysis of all children having lung resection for congenital lesions at our institution between 1997 and 2004. Data were collected from analysis of case notes, operative records and clinical consultation. The mean follow-up was 37.95 months. The data were analyzed using SPSS. Results: Forty-one children (13 F/28 M underwent major lung resections during the study period. Their median age was 4.66 months (1 day-9 years. The resected lesions included 21 congenital cystic adenomatoid malformations, 14 congenital lobar emphysema, four sequestrations and one bronchogenic cyst. Fifty percent of the lesions were diagnosed antenatally. Twenty-six patients had a complete lobectomy while 15 patients had parenchymal sparing resection of the lesion alone. Mean postoperative stay was 5.7 days. There have been no complications in any of the patients. All patients are currently alive, asymptomatic and well. None of the patients have any significant chest deformity. Conclusions: We conclude that open lung resection enables parenchymal sparing surgery, is versatile, has few complications and produces very good long-term results. It remains the "gold standard" against which minimally invasive techniques may be judged.

  18. Robotic vascular resections during Whipple procedure

    OpenAIRE

    Allan, Bassan J.; Novak, Stephanie M.; Hogg, Melissa E.; Zeh, Herbert J.

    2018-01-01

    Indications for resection of pancreatic cancers have evolved to include selected patients with involvement of peri-pancreatic vascular structures. Open Whipple procedures have been the standard approach for patients requiring reconstruction of the portal vein (PV) or superior mesenteric vein (SMV). Recently, high-volume centers are performing minimally invasive Whipple procedures with portovenous resections. Our institution has performed seventy robotic Whipple procedures with concomitant vas...

  19. Morphometrical differences between resectable and non-resectable pancreatic cancer: a fractal analysis.

    Science.gov (United States)

    Vasilescu, Catalin; Giza, Dana Elena; Petrisor, Petre; Dobrescu, Radu; Popescu, Irinel; Herlea, Vlad

    2012-01-01

    Pancreatic cancer is a highly aggressive cancer with a rising incidence and poor prognosis despite active surgical treatment. Candidates for surgical resection should be carefully selected. In order to avoid unnecessary laparotomy it is useful to identify reliable factors that may predict resectability. Nuclear morphometry and fractal dimension of pancreatic nuclear features could provide important preoperative information in assessing pancreas resectability. Sixty-one patients diagnosed with pancreatic cancer were enrolled in this retrospective study between 2003 and 2005. Patients were divided into two groups: one resectable cancer group and one with non-resectable pancreatic cancer. Morphometric parameters measured were: nuclear area, length of minor axis and length of major axis. Nuclear shape and chromatin distribution of the pancreatic tumor cells were both estimated using fractal dimension. Morphometric measurements have shown significant differences between the nuclear area of the resectable group and the non-resectable group (61.9 ± 19.8µm vs. 42.2 ± 15.6µm). Fractal dimension of the nuclear outlines and chromatin distribution was found to have a higher value in the non-resectable group (p<0.05). Objective measurements should be performed to improve risk assessment and therapeutic decisions in pancreatic cancer. Nuclear morphometry of the pancreatic nuclear features can provide important pre-operative information in resectability assessment. The fractal dimension of the nuclear shape and chromatin distribution may be considered a new promising adjunctive tool for conventional pathological analysis.

  20. Pathological features of olfactory neuroblastoma in an axolotl (Ambystoma mexicanum).

    Science.gov (United States)

    Shioda, Chieko; Uchida, Kazuyuki; Nakayama, Hiroyuki

    2011-08-01

    A one-year-old, female Mexican axolotl (Ambystoma mexicanum) had a rough-surfaced, polypoid, pink tumor mass of approximately 10 mm in diameter in the oral cavity. Histologically, the tumor extended from the ethmoturbinate region and into the oral cavity and had replaced some of the maxillary bone tissue. The tumor mass was composed of a lobular architecture of small round-shaped tumor cells with occasional Flexner-Wintersteiner-like rosette formation. There were no metastatic lesions in the other organs. Immunohistochemically, the tumor cells were partly positive for several neural markers (class III beta-tubulin, S-100 protein, and doublecortin) and intensely positive for an epithelial marker (cytokeratin AE1/AE3). These results suggest that the present tumor originated from neuroectodermal tissue. Considering the location and histological and immunohistochemical features of the tumor, a diagnosis of olfactory neuroblastoma was made.

  1. Neuroblastoma in a patient with Coffin-Siris syndrome.

    Science.gov (United States)

    Pollono, Daniel; Drut, Ricardo; Cecotti, Norma; Pollono, Agustina

    2009-01-01

    We report the case of an 8-year-old boy with the phenotypic features of Coffin-Siris syndrome diffuse hypertrichosis, flat occiput, scant scalp hair, flat supraorbital arch, triangular eyebrows, horizontal palpebral fissure, anteverted nares, triangular philtrum, coarse lips, high-arched palate, micrognathia, low set and dorsaly rotated ears, short neck, wide thorax, widely set nipples, transverse palmar crease, psychomotor delay, urinary malformations (paraurethral diverticulum, hypoplasia of left kidney associated with vesicoureteral reflux grade 3-4), bilateral inguinal hernia, and dorsolumbar kyphoscoliosis. In the follow-up he presented a retroperitoneal neuroblastoma. Although this type of tumor has been referred to develop in several genetic and mutimalformative syndromes, it seems that present association has not been previously reported.

  2. Cell cycle control by the thyroid hormone in neuroblastoma cells

    International Nuclear Information System (INIS)

    Garcia-Silva, Susana; Perez-Juste, German; Aranda, Ana

    2002-01-01

    The thyroid hormone (T3) blocks proliferation and induces differentiation of neuroblastoma N2a-β cells that overexpress the β1 isoform of the T3 receptor. An element in the region responsible for premature termination of transcription mediates a rapid repression of c-myc gene expression by T3. The hormone also causes a decrease of cyclin D1 gene transcription, and is able to antagonize the activation of the cyclin D1 promoter by Ras. In addition, a strong and sustained increase of the levels of the cyclin kinase inhibitor (CKI) p27 Kip1 are found in T3-treated cells. The increased levels of p27 Kip1 lead to a marked inhibition of the kinase activity of the cyclin-CDK2 complexes. As a consequence of these changes, retinoblastoma proteins are hypophosphorylated in T3-treated N2a-β cells, and progression through the restriction point in the cell cycle is blocked

  3. Dielectrophoretic capture and genetic analysis of single neuroblastoma tumor cells

    Directory of Open Access Journals (Sweden)

    Erica L Carpenter

    2014-07-01

    Full Text Available Our understanding of the diversity of cells that escape the primary tumor and seed micrometastases remains rudimentary, and approaches for studying circulating and disseminated tumor cells have been limited by low throughput and sensitivity, reliance on single parameter sorting, and a focus on enumeration rather than phenotypic and genetic characterization. Here we utilize a highly sensitive microfluidic and dielectrophoretic approach for the isolation and genetic analysis of individual tumor cells. We employed fluorescence labeling to isolate 208 single cells from spiking experiments conducted with 11 cell lines, including 8 neuroblastoma cell lines, and achieved a capture sensitivity of 1 tumor cell per 106 white blood cells. Sample fixation or freezing had no detectable effect on cell capture. Point mutations were accurately detected in the whole genome amplification product of captured single tumor cells but not in negative control white blood cells. We applied this approach to capture 144 single tumor cells from 10 bone marrow samples from patients suffering from neuroblastoma. In this pediatric malignancy, high-risk patients often exhibit wide-spread hematogenous metastasis, but access to primary tumor can be difficult or impossible. Here we used flow-based sorting to pre-enrich samples with tumor involvement below 0.02%. For all patients for whom a mutation in the Anaplastic Lymphoma Kinase gene had already been detected in their primary tumor, the same mutation was detected in single cells from their marrow. These findings demonstrate a novel, non-invasive, and adaptable method for the capture and genetic analysis of single tumor cells from cancer patients.

  4. In vitro assessment of curcumin against murine neuroblastoma cells.

    Science.gov (United States)

    Vanisree, Arambakkam Janardhanam; Ramanan, Ramya

    2007-04-01

    Neuroblastoma (NB) is a well-known malignant disease in infants, which comprises 10% of childhood malignancies. Despite recent advances in understanding the neuro-oncology, NB still accounts for more death in childhood than any other cancer. Research in childhood tumors should not only be focused on the malignant signatures of cancer cells but also novel drug prototypes using phytochemicals. The present study was aimed to determine the role of curcumin against murine neuroblastoma cell line (N2a). The in vitro assessment of curcumin against was made in N2a cell line in a dose-dependent manner (group I (control) and group II - IX (10 microM-80 microM). The efficacy of the drug was evaluated by estimating the levels of protein bound carbohydrates, glycoprotein, genomic DNA, total RNA levels, and inhibition of MMP-9 were studied. The gap junctional communication in the cells was also assessed. The levels of protein bound carbohydrates, DNA, RNA levels, glycoprotein were found to be altered on drug supplementation in NB cells. Inhibition of MMP-9 in curcumin-supplemented N2a cells was revealed by zymographic analysis. Assessment of Lucifer yellow dye uptake in curcumin-supplemented N2a cells showed the up-regulation of GJIC. These observations suggest that the curcumin, the active principle of curcuma longa, could be developed into an effective chemo preventive and chemotherapeutic agent. This selected concentration range needs further studies at molecular level, for conforming its role and its action against uncontrolled proliferation of NB.

  5. A 6-gene signature identifies four molecular subgroups of neuroblastoma

    LENUS (Irish Health Repository)

    Abel, Frida

    2011-04-14

    Abstract Background There are currently three postulated genomic subtypes of the childhood tumour neuroblastoma (NB); Type 1, Type 2A, and Type 2B. The most aggressive forms of NB are characterized by amplification of the oncogene MYCN (MNA) and low expression of the favourable marker NTRK1. Recently, mutations or high expression of the familial predisposition gene Anaplastic Lymphoma Kinase (ALK) was associated to unfavourable biology of sporadic NB. Also, various other genes have been linked to NB pathogenesis. Results The present study explores subgroup discrimination by gene expression profiling using three published microarray studies on NB (47 samples). Four distinct clusters were identified by Principal Components Analysis (PCA) in two separate data sets, which could be verified by an unsupervised hierarchical clustering in a third independent data set (101 NB samples) using a set of 74 discriminative genes. The expression signature of six NB-associated genes ALK, BIRC5, CCND1, MYCN, NTRK1, and PHOX2B, significantly discriminated the four clusters (p < 0.05, one-way ANOVA test). PCA clusters p1, p2, and p3 were found to correspond well to the postulated subtypes 1, 2A, and 2B, respectively. Remarkably, a fourth novel cluster was detected in all three independent data sets. This cluster comprised mainly 11q-deleted MNA-negative tumours with low expression of ALK, BIRC5, and PHOX2B, and was significantly associated with higher tumour stage, poor outcome and poor survival compared to the Type 1-corresponding favourable group (INSS stage 4 and\\/or dead of disease, p < 0.05, Fisher\\'s exact test). Conclusions Based on expression profiling we have identified four molecular subgroups of neuroblastoma, which can be distinguished by a 6-gene signature. The fourth subgroup has not been described elsewhere, and efforts are currently made to further investigate this group\\'s specific characteristics.

  6. Irradiation spine deformity in children treated for neuroblastoma

    International Nuclear Information System (INIS)

    Mayfield, J.K.; Riseborough, E.J.; Nehme, M.

    1978-01-01

    A retrospective long-term follow-up review of 56 children with neuroblastoma surviving five years and longer following treatment since 1946 revealed that 57% had developed spine deformity (S.D.) following treatment with 250 kilovolt irradiation at the time of review. The average age at diagnosis was 17 months. Irradiation therapy was delivered to most children before 24 months of age. Follow-up averaged 12.9 years with a range of 5-31 years. Eighty-five per cent of the children had developed structural spine deformity at skeletal maturity and 54% of these children had scoliosis greater than 20 degrees. Sixteen per cent of irradiated children developed structural kyphosis. Non-midline opposing anterior and posterior ports were used most frequently. Mean dosage in patients who developed scoliosis of 20 degrees or more was 3588 rads (spine dosage) and 3746 rads in patients who developed kyphosis. Irradiation through opposing anterior and posterior ports was more commonly associated with the development of S.D. Sixty-six per cent of children who had more than 2000 rads developed S.D. The adolescent growth spurt was associated with an increase in the frequency and severity of spine deformity. This study indicated that moderate to severe S.D. was produced by irradiation in excess of 2000 rads administered with a 250-kilovoltage machine. This study would also suggest that children with neuroblastoma treated with orthovoltage irradiation should be followed closely by the orthopaedic surgeon, the oncologist, the radiotherapist and the paediatrician until the completion of skeletal growth for the development of unsightly structural spine deformity. Early bracing and surgery may be helpful in controlling these deformities in the pre-adolescent to early adolescent years. Continued observation is necessary to determine if current irradiation techniques will minimize or eradicate the incidence and severity of these complications. (author)

  7. Flows and Stratification of an Enclosure Containing Both Localised and Vertically Distributed Sources of Buoyancy

    Science.gov (United States)

    Partridge, Jamie; Linden, Paul

    2013-11-01

    We examine the flows and stratification established in a naturally ventilated enclosure containing both a localised and vertically distributed source of buoyancy. The enclosure is ventilated through upper and lower openings which connect the space to an external ambient. Small scale laboratory experiments were carried out with water as the working medium and buoyancy being driven directly by temperature differences. A point source plume gave localised heating while the distributed source was driven by a controllable heater mat located in the side wall of the enclosure. The transient temperatures, as well as steady state temperature profiles, were recorded and are reported here. The temperature profiles inside the enclosure were found to be dependent on the effective opening area A*, a combination of the upper and lower openings, and the ratio of buoyancy fluxes from the distributed and localised source Ψ =Bw/Bp . Industrial CASE award with ARUP.

  8. Neuromorphic Audio-Visual Sensor Fusion on a Sound-Localising Robot

    Directory of Open Access Journals (Sweden)

    Vincent Yue-Sek Chan

    2012-02-01

    Full Text Available This paper presents the first robotic system featuring audio-visual sensor fusion with neuromorphic sensors. We combine a pair of silicon cochleae and a silicon retina on a robotic platform to allow the robot to learn sound localisation through self-motion and visual feedback, using an adaptive ITD-based sound localisation algorithm. After training, the robot can localise sound sources (white or pink noise in a reverberant environment with an RMS error of 4 to 5 degrees in azimuth. In the second part of the paper, we investigate the source binding problem. An experiment is conducted to test the effectiveness of matching an audio event with a corresponding visual event based on their onset time. The results show that this technique can be quite effective, despite its simplicity.

  9. Deconfinement, chiral transition and localisation in a QCD-like model

    Energy Technology Data Exchange (ETDEWEB)

    Giordano, Matteo; Katz, Sándor D. [Institute for Theoretical Physics, Eötvös University,Pázmány P. sétány 1/A, H-1117 Budapest (Hungary); MTA-ELTE “Lendület” Lattice Gauge Theory Research Group,Pázmány P. sétány 1/A, H-1117 Budapest (Hungary); Kovács, Tamás G. [Institute for Nuclear Research of the Hungarian Academy of Sciences,Bem tér 18/c, H-4026 Debrecen (Hungary); Pittler, Ferenc [HISKP(Theory), University of Bonn,Nussallee 14-16, D-53115 Bonn (Germany)

    2017-02-10

    We study the problems of deconfinement, chiral symmetry restoration and localisation of the low Dirac eigenmodes in a toy model of QCD, namely unimproved staggered fermions on lattices of temporal extension N{sub T}=4. This model displays a genuine deconfining and chirally-restoring first-order phase transition at some critical value of the gauge coupling. Our results indicate that the onset of localisation of the lowest Dirac eigenmodes takes place at the same critical coupling where the system undergoes the first-order phase transition. This provides further evidence of the close relation between deconfinement, chiral symmetry restoration and localisation of the low modes of the Dirac operator on the lattice.

  10. Towards a Multimodal Methodology for the Analysis of Translated/Localised Games

    Directory of Open Access Journals (Sweden)

    Bárbara Resende Coelho

    2016-12-01

    Full Text Available Multimedia materials require research methodologies that are able to comprehend all of their assets. Videogames are the epitome of multimedia, joining image, sound, video, animation, graphics and text with the interactivity factor. A methodology to conduct research into translation and localisation of videogames should be able to analyse all of its assets and features. This paper sets out to develop a research methodology for games and their translations/localisations that goes beyond the collection and analysis of “screenshots” and includes as many of their assets as possible. Using the fully localised version of the game Watchdogs, this papers shows how tools and technologies allow for transcending the mere analysis of linguistic contents within multimedia materials. Using software ELAN Language Archive to analyse Portuguese-language dubbed and English-language subtitled excerpts from the videogame, it was possible to identify patterns in both linguistic and audio-visual elements, as well as to correlate them.

  11. Interdependency of formation and localisation of the Min complex controls symmetric plastid division.

    Science.gov (United States)

    Maple, Jodi; Møller, Simon G

    2007-10-01

    Plastid division represents a fundamental biological process essential for plant development; however, the molecular basis of symmetric plastid division is unclear. AtMinE1 plays a pivotal role in selection of the plastid division site in concert with AtMinD1. AtMinE1 localises to discrete foci in chloroplasts and interacts with AtMinD1, which shows a similar localisation pattern. Here, we investigate the importance of Min protein complex formation during the chloroplast division process. Dissection of the assembly of the Min protein complex and determination of the interdependency of complex assembly and localisation in planta allow us to present a model of the molecular basis of selection of the division site in plastids. Moreover, functional analysis of AtMinE1 in bacteria demonstrates the level of functional conservation and divergence of the plastidic MinE proteins.

  12. Selection of optimal therapy for neuroblastoma: a study of the immunomodulatory effects of surgery and irradiation in the murine C1300 neuroblastoma model

    International Nuclear Information System (INIS)

    Topalian, S.L.; Ziegler, M.M.

    1987-01-01

    Human neuroblastoma is an immunogenic tumor for which therapy directed in an immunologic context may offer some advantage over conventional treatment. This study examines the immunomodulatory effects of surgery and irradiation in the murine C1300 neuroblastoma model. In vivo studies of primary tumor growth characteristics after treatment demonstrated no superiority of either therapeutic modality in control of local tumor or prolongation of host survival. However, irradiated hosts showed an increased ability to reject a secondary tumor challenge, compared to their surgical counterparts. That this phenomenon may be immune-related is suggested by in vitro studies of T lymphocyte function utilizing mixed lymphocyte-tumor cell cultures and PHA lymphoblastogenesis

  13. Techniques avancées du traitement d'antennes pour la localisation de sources : application à la localisation de mobile: cas du système UMTS.

    OpenAIRE

    Grosicki , Emmanuele

    2003-01-01

    La thèse a porté sur la localisation de mobile pour les systèmes UMTS-FDD. Il s'agit d'un sujet qui intéresse de plus en plus les opérateurs, notamment dans le cas de système UMTS-FDD où il existe très peu de réseaux réels. Les différentes approches permettant de localiser un émetteur ont ainsi été envisagées, et plus particulièrement, celles basées sur les mesures de puissances, les temps d'arrivée (TOA) en liaison descendante ou encore celles basées sur les angles d'arrivée (AOA) et sur tou...

  14. Divergent RNA Localisation Patterns of Maternal Genes Regulating Embryonic Patterning in the Butterfly Pararge aegeria.

    Directory of Open Access Journals (Sweden)

    Jean-Michel Carter

    Full Text Available The maternal effect genes responsible for patterning the embryo along the antero-posterior (AP axis are broadly conserved in insects. The precise function of these maternal effect genes is the result of the localisation of their mRNA in the oocyte. The main developmental mechanisms involved have been elucidated in Drosophila melanogaster, but recent studies have shown that other insect orders often diverge in RNA localisation patterns. A recent study has shown that in the butterfly Pararge aegeria the distinction between blastodermal embryonic (i.e. germ band and extra-embryonic tissue (i.e. serosa is already specified in the oocyte during oogenesis in the ovariole, long before blastoderm cellularisation. To examine the extent by which a female butterfly specifies and patterns the AP axis within the region fated to be the germ band, and whether she specifies a germ plasm, we performed in situ hybridisation experiments on oocytes in P. aegeria ovarioles and on early embryos. RNA localisation of the following key maternal effect genes were investigated: caudal (cad, orthodenticle (otd, hunchback (hb and four nanos (nos paralogs, as well as TDRD7 a gene containing a key functional domain (OST-HTH/LOTUS shared with oskar. TDRD7 was mainly confined to the follicle cells, whilst hb was exclusively zygotically transcribed. RNA of some of the nos paralogs, otd and cad revealed complex localisation patterns within the cortical region prefiguring the germ band (i.e. germ cortex. Rather interestingly, otd was localised within and outside the anterior of the germ cortex. Transcripts of nos-O formed a distinct granular ring in the middle of the germ cortex possibly prefiguring the region where germline stem cells form. These butterfly RNA localisation patterns are highly divergent with respect to other insects, highlighting the diverse ways in which different insect orders maternally regulate early embryogenesis of their offspring.

  15. Divergent RNA Localisation Patterns of Maternal Genes Regulating Embryonic Patterning in the Butterfly Pararge aegeria

    Science.gov (United States)

    Carter, Jean-Michel; Gibbs, Melanie; Breuker, Casper J.

    2015-01-01

    The maternal effect genes responsible for patterning the embryo along the antero-posterior (AP) axis are broadly conserved in insects. The precise function of these maternal effect genes is the result of the localisation of their mRNA in the oocyte. The main developmental mechanisms involved have been elucidated in Drosophila melanogaster, but recent studies have shown that other insect orders often diverge in RNA localisation patterns. A recent study has shown that in the butterfly Pararge aegeria the distinction between blastodermal embryonic (i.e. germ band) and extra-embryonic tissue (i.e. serosa) is already specified in the oocyte during oogenesis in the ovariole, long before blastoderm cellularisation. To examine the extent by which a female butterfly specifies and patterns the AP axis within the region fated to be the germ band, and whether she specifies a germ plasm, we performed in situ hybridisation experiments on oocytes in P. aegeria ovarioles and on early embryos. RNA localisation of the following key maternal effect genes were investigated: caudal (cad), orthodenticle (otd), hunchback (hb) and four nanos (nos) paralogs, as well as TDRD7 a gene containing a key functional domain (OST-HTH/LOTUS) shared with oskar. TDRD7 was mainly confined to the follicle cells, whilst hb was exclusively zygotically transcribed. RNA of some of the nos paralogs, otd and cad revealed complex localisation patterns within the cortical region prefiguring the germ band (i.e. germ cortex). Rather interestingly, otd was localised within and outside the anterior of the germ cortex. Transcripts of nos-O formed a distinct granular ring in the middle of the germ cortex possibly prefiguring the region where germline stem cells form. These butterfly RNA localisation patterns are highly divergent with respect to other insects, highlighting the diverse ways in which different insect orders maternally regulate early embryogenesis of their offspring. PMID:26633019

  16. Localised sarcoptic mange in dogs: a retrospective study of 10 cases.

    Science.gov (United States)

    Pin, D; Bensignor, E; Carlotti, D-N; Cadiergues, M C

    2006-10-01

    The authors report 10 cases of localised sarcoptic mange in dogs. In each case, lesions were localised to one precise area of the skin. Pruritus was present in nine cases and absent in one. Affected areas were the feet (one case), the face and/or the pinnae (six cases), the abdominal skin (one case), the flank (one case) and the lumbar area (one case). The types of lesions were erythema, papules, lichenification, scales, crusts and alopecia. Parasites were found in all cases except one, in which anti-immunoglobulin G Sarcoptes serology was positive. The acaricidal treatments given were lindane, ivermectin or selamectin and were all successful.

  17. Localisation of lung cancer by a radiolabelled monoclonal antibody against the c-myc oncogene product

    Energy Technology Data Exchange (ETDEWEB)

    Chan, S Y.T.; Evan, G I; Ritson, A; Watson, J; Wraight, P; Sikora, K

    1986-11-01

    A set of mouse monoclonal antibodies against the c-myc oncogene product, a 62,000 dalton nuclear binding protein involved in cell cycle control, has been constructed by immunisation with synthetic peptide fragments. One such antibody, CT14, was radiolabelled with /sup 131/I and administered to 20 patients with different malignant diseases. Good tumour localisation was observed in 12 out of 14 patients with primary bronchial carcinoma but not in patients with pulmonary metastases from primary tumours elsewhere. Successfully localised tumours were all 3 cm or more in diameter. Monoclonal antibodies against oncogene products may provide novel selective tools for the diagnosis and therapy of cancer.

  18. Accuracy of target localisation and alignment in stereotactic radiosurgery at Royal Prince Alfred Hospital

    International Nuclear Information System (INIS)

    Downes, S.

    1996-01-01

    Full text: Over the last 30 years, stereotactic radiosurgery has become an effective clinical tool in the treatment of intra-cranial lesions. The use of high doses to a specific target volume in a single fraction and the proximity of critical organs requires very accurate geometric localisation of the various cranial structures (using CT, MRI and angiography imaging) and accurate alignment of the target volume prior to treatment. The purpose of this paper was to determine the accuracy of localising cranial structures using computed tomography and angiographic imaging modalities and to determine the accuracy of aligning the treatment isocentre to the specified coordinates. The sum of these two errors will give the total deviation of the treated target from the actual target. Measurements were made using an anthropomorphic (ART) phantom of an adult male and a cerrobend target. The ART phantom was immobilised using the Brown-Roberts-Wells (BRW) ring. The cerrobend target was inserted into the skull at 10 different positions. Each of these 10 positions were scanned using CT and angiographic imaging and localised using the stereotactic planning software. For each test position, the ART phantom was placed on the treatment couch and aligned to the treatment coordinates determined using localisation (CT and angiography). A-P and lateral port films were then made of the target. The distance between the centre of the cerrobend target (intended target) and the centre of radiation (actual target) was the total error in localisation and alignment of the target. For computed tomography, the measurements showed the average error in localisation and alignment of the target was ±0.7mm. In terms of coordinate axis, the average error was: A-P axis = ±0.5mm, Lateral(left-right) Axis = ±0.3mm, Vertical(inferior superior) Axis ±0.4mm. From these measurements it was shown that using the stereotactic radiosurgery planning system and hardware, cranial lesions could be localised and

  19. Strain localisation in mechanically layered rocks beneath detachment zones: insights from numerical modelling

    Directory of Open Access Journals (Sweden)

    L. Le Pourhiet

    2013-04-01

    Full Text Available We have designed a series of fully dynamic numerical simulations aimed at assessing how the orientation of mechanical layering in rocks controls the orientation of shear bands and the depth of penetration of strain in the footwall of detachment zones. Two parametric studies are presented. In the first one, the influence of stratification orientation on the occurrence and mode of strain localisation is tested by varying initial dip of inherited layering in the footwall with regard to the orientation of simple shear applied at the rigid boundary simulating a rigid hanging wall, all scaling and rheological parameter kept constant. It appears that when Mohr–Coulomb plasticity is being used, shear bands are found to localise only when the layering is being stretched. This corresponds to early deformational stages for inital layering dipping in the same direction as the shear is applied, and to later stages for intial layering dipping towards the opposite direction of shear. In all the cases, localisation of the strain after only γ=1 requires plastic yielding to be activated in the strong layer. The second parametric study shows that results are length-scale independent and that orientation of shear bands is not sensitive to the viscosity contrast or the strain rate. However, decreasing or increasing strain rate is shown to reduce the capacity of the shear zone to localise strain. In the later case, the strain pattern resembles a mylonitic band but the rheology is shown to be effectively linear. Based on the results, a conceptual model for strain localisation under detachment faults is presented. In the early stages, strain localisation occurs at slow rates by viscous shear instabilities but as the layered media is exhumed, the temperature drops and the strong layers start yielding plastically, forming shear bands and localising strain at the top of the shear zone. Once strain localisation has occured, the deformation in the shear band becomes

  20. Transcallosal, Transchoroidal Resection of a Recurrent Craniopharyngioma.

    Science.gov (United States)

    Jean, Walter C

    2018-04-01

    Objective  To demonstrate the transchoroidal approach for the resection of a recurrent craniopharyngioma. Design  Video case report. Setting  Microsurgical resection. Participant  The patient was a 27-year-old woman with a history of a craniopharyngioma, resected twice during the year prior to presentation to our unit. Both operations were done via the left anterolateral corridor, and afterward, she was blind in the left eye and was treated with Desmopressin (DDAVP) for diabetes insipidus (DI). Serial magnetic resonance imaging (MRI) showed progression of the tumor residual, and she was referred for further surgical intervention. Main Outcome Measures  Pre- and postoperative MRIs measured the degree of resection. Results  For this, her third surgery, a transcallosal, transchoroidal approach, was chosen to offer the widest possible exposure. Given her history, an aggressive total resection was the best strategy. The patient was placed supine with the head neutral. A right frontal craniotomy allowed access to the interhemispheric fissure. By opening the corpus callosum, the left lateral ventricle was entered. The transchoroidal approach started with dissection of the tenia fornicis to open the choroidal fissure. After this, sufficient exposure to the posterior parts of the tumor was gained. Resection proceeded to the bottom of the tumor, exposing the basilar apex and interpeduncular cistern, and continued back anteriorly. In the end, a microscopic total resection was achieved. With a long hospital stay to treat her brittle DI, the patient slowly returned to neurological baseline. Conclusion  The transchoroidal approach is an effective way to remove large tumors in the third ventricle. The link to the video can be found at: https://youtu.be/2-Aqjaay8dg .

  1. Clinical potentials of methylator phenotype in stage 4 high-risk neuroblastoma: an open challenge.

    Directory of Open Access Journals (Sweden)

    Barbara Banelli

    Full Text Available Approximately 20% of stage 4 high-risk neuroblastoma patients are alive and disease-free 5 years after disease onset while the remaining experience rapid and fatal progression. Numerous findings underline the prognostic role of methylation of defined target genes in neuroblastoma without taking into account the clinical and biological heterogeneity of this disease. In this report we have investigated the methylation of the PCDHB cluster, the most informative member of the "Methylator Phenotype" in neuroblastoma, hypothesizing that if this epigenetic mark can predict overall and progression free survival in high-risk stage 4 neuroblastoma, it could be utilized to improve the risk stratification of the patients, alone or in conjunction with the previously identified methylation of the SFN gene (14.3.3sigma that can accurately predict outcome in these patients. We have utilized univariate and multivariate models to compare the prognostic power of PCDHB methylation in terms of overall and progression free survival, quantitatively determined by pyrosequencing, with that of other markers utilized for the patients' stratification utilizing methylation thresholds calculated on neuroblastoma at stage 1-4 and only on stage 4, high-risk patients. Our results indicate that PCDHB accurately distinguishes between high- and intermediate/low risk stage 4 neuroblastoma in agreement with the established risk stratification criteria. However PCDHB cannot predict outcome in the subgroup of stage 4 patients at high-risk whereas methylation levels of SFN are suggestive of a "methylation gradient" associated with tumor aggressiveness as suggested by the finding of a higher threshold that defines a subset of patients with an extremely severe disease (OS <24 months. Because of the heterogeneity of neuroblastoma we believe that clinically relevant methylation markers should be selected and tested on homogeneous groups of patients rather than on patients at all stages.

  2. Cyclin-Dependent Kinase Inhibitor AT7519 as a Potential Drug for MYCN-Dependent Neuroblastoma.

    Science.gov (United States)

    Dolman, M Emmy M; Poon, Evon; Ebus, Marli E; den Hartog, Ilona J M; van Noesel, Carel J M; Jamin, Yann; Hallsworth, Albert; Robinson, Simon P; Petrie, Kevin; Sparidans, Rolf W; Kok, Robbert J; Versteeg, Rogier; Caron, Huib N; Chesler, Louis; Molenaar, Jan J

    2015-11-15

    MYCN-dependent neuroblastomas have low cure rates with current multimodal treatment regimens and novel therapeutic drugs are therefore urgently needed. In previous preclinical studies, we have shown that targeted inhibition of cyclin-dependent kinase 2 (CDK2) resulted in specific killing of MYCN-amplified neuroblastoma cells. This study describes the in vivo preclinical evaluation of the CDK inhibitor AT7519. Preclinical drug testing was performed using a panel of MYCN-amplified and MYCN single copy neuroblastoma cell lines and different MYCN-dependent mouse models of neuroblastoma. AT7519 killed MYCN-amplified neuroblastoma cell lines more potently than MYCN single copy cell lines with a median LC50 value of 1.7 compared to 8.1 μmol/L (P = 0.0053) and a significantly stronger induction of apoptosis. Preclinical studies in female NMRI homozygous (nu/nu) mice with neuroblastoma patient-derived MYCN-amplified AMC711T xenografts revealed dose-dependent growth inhibition, which correlated with intratumoral AT7519 levels. CDK2 target inhibition by AT7519 was confirmed by significant reductions in levels of phosphorylated retinoblastoma (p-Rb) and nucleophosmin (p-NPM). AT7519 treatment of Th-MYCN transgenic mice resulted in improved survival and clinically significant tumor regression (average tumor size reduction of 86% at day 7 after treatment initiation). The improved efficacy of AT7519 observed in Th-MYCN mice correlated with higher tumor exposure to the drug. This study strongly suggests that AT7519 is a promising drug for the treatment of high-risk neuroblastoma patients with MYCN amplification. ©2015 American Association for Cancer Research.

  3. MYCN and HDAC5 transcriptionally repress CD9 to trigger invasion and metastasis in neuroblastoma.

    Science.gov (United States)

    Fabian, Johannes; Opitz, Desirée; Althoff, Kristina; Lodrini, Marco; Hero, Barbara; Volland, Ruth; Beckers, Anneleen; de Preter, Katleen; Decock, Anneleen; Patil, Nitin; Abba, Mohammed; Kopp-Schneider, Annette; Astrahantseff, Kathy; Wünschel, Jasmin; Pfeil, Sebastian; Ercu, Maria; Künkele, Annette; Hu, Jamie; Thole, Theresa; Schweizer, Leonille; Mechtersheimer, Gunhild; Carter, Daniel; Cheung, Belamy B; Popanda, Odilia; von Deimling, Andreas; Koster, Jan; Versteeg, Rogier; Schwab, Manfred; Marshall, Glenn M; Speleman, Frank; Erb, Ulrike; Zoeller, Margot; Allgayer, Heike; Simon, Thorsten; Fischer, Matthias; Kulozik, Andreas E; Eggert, Angelika; Witt, Olaf; Schulte, Johannes H; Deubzer, Hedwig E

    2016-10-11

    The systemic and resistant nature of metastatic neuroblastoma renders it largely incurable with current multimodal treatment. Clinical progression stems mainly from the increasing burden of metastatic colonization. Therapeutically inhibiting the migration-invasion-metastasis cascade would be of great benefit, but the mechanisms driving this cycle are as yet poorly understood. In-depth transcriptome analyses and ChIP-qPCR identified the cell surface glycoprotein, CD9, as a major downstream player and direct target of the recently described GRHL1 tumor suppressor. CD9 is known to block or facilitate cancer cell motility and metastasis dependent upon entity. High-level CD9 expression in primary neuroblastomas correlated with patient survival and established markers for favorable disease. Low-level CD9 expression was an independent risk factor for adverse outcome. MYCN and HDAC5 colocalized to the CD9 promoter and repressed transcription. CD9 expression diminished with progressive tumor development in the TH-MYCN transgenic mouse model for neuroblastoma, and CD9 expression in neuroblastic tumors was far below that in ganglia from wildtype mice. Primary neuroblastomas lacking MYCN amplifications displayed differential CD9 promoter methylation in methyl-CpG-binding domain sequencing analyses, and high-level methylation was associated with advanced stage disease, supporting epigenetic regulation. Inducing CD9 expression in a SH-EP cell model inhibited migration and invasion in Boyden chamber assays. Enforced CD9 expression in neuroblastoma cells transplanted onto chicken chorioallantoic membranes strongly reduced metastasis to embryonic bone marrow. Combined treatment of neuroblastoma cells with HDAC/DNA methyltransferase inhibitors synergistically induced CD9 expression despite hypoxic, metabolic or cytotoxic stress. Our results show CD9 is a critical and indirectly druggable suppressor of the invasion-metastasis cycle in neuroblastoma.

  4. Comparison of Clinico-Radiological Features between Congenital Cystic Neuroblastoma and Neonatal Adrenal Hemorrhagic Pseudocyst

    Energy Technology Data Exchange (ETDEWEB)

    Eo, Hong; Kim, Ji Hye; Jang, Kyung Mi; Yoo, So Young [Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Lim, Gye Yeon [St. Mary' s Hospital Catholic University, Seoul (Korea, Republic of); Kim, Myung Joon [Severance Hospital Yonsei University, Seoul (Korea, Republic of); Kim, Ok Hwa [Ajou University Hospital, Suwon (Korea, Republic of)

    2011-02-15

    To evaluate the radiological and clinical findings of congenital cystic neuroblastomas as compared with those of the cystic presentation of neonatal adrenal hemorrhage. We analyzed the US (n = 52), CT (n = 24), and MR (n = 4) images as well as the medical records of 28 patients harboring congenital cystic neuroblastomas (n = 16) and neonatal adrenal hemorrhagic pseudocysts (n = 14). The history of prenatal detection, location, size, presence of outer wall enhancement, internal septations, solid portion, calcification, turbidity, vascular flow on a Doppler examination, and evolution patterns were compared in two groups of cystic lesions, by Fischer's exact test. All (100%) neuroblastomas and three (21%) of the 14 hemorrhagic pseudocysts were detected prenatally. Both groups of cystic lesions occurred more frequently on the right side; 11 of 16 (69%) for neuroblastomas and 11 of 14 (79%) for hemorrhagic pseudocysts. The size, presence of solid portion, septum, enhancement, and turbidity did not differ significantly (p > 0.05) between the two groups of cystic lesions. However, tiny calcifications (n = 3) and vascular flow on color Doppler US (n = 3) were noted in only neuroblastomas. The cystic neuroblastomas became complex solid and cystic masses, and did not disappear for up to 90 days in the three following cases, whereas 11 of the 14 (79%) hemorrhagic pseudocysts disappeared completely and the three remaining (27%) evolved to calcifications only. Although the imaging findings of two groups of cystic lesions were similar, prenatal detection, the presence of calcification on initial images, vascularity on color Doppler US, and evolution to a more complex mass may all favor neuroblastomas

  5. Comparison of Clinico-Radiological Features between Congenital Cystic Neuroblastoma and Neonatal Adrenal Hemorrhagic Pseudocyst

    International Nuclear Information System (INIS)

    Eo, Hong; Kim, Ji Hye; Jang, Kyung Mi; Yoo, So Young; Lim, Gye Yeon; Kim, Myung Joon; Kim, Ok Hwa

    2011-01-01

    To evaluate the radiological and clinical findings of congenital cystic neuroblastomas as compared with those of the cystic presentation of neonatal adrenal hemorrhage. We analyzed the US (n = 52), CT (n = 24), and MR (n = 4) images as well as the medical records of 28 patients harboring congenital cystic neuroblastomas (n = 16) and neonatal adrenal hemorrhagic pseudocysts (n = 14). The history of prenatal detection, location, size, presence of outer wall enhancement, internal septations, solid portion, calcification, turbidity, vascular flow on a Doppler examination, and evolution patterns were compared in two groups of cystic lesions, by Fischer's exact test. All (100%) neuroblastomas and three (21%) of the 14 hemorrhagic pseudocysts were detected prenatally. Both groups of cystic lesions occurred more frequently on the right side; 11 of 16 (69%) for neuroblastomas and 11 of 14 (79%) for hemorrhagic pseudocysts. The size, presence of solid portion, septum, enhancement, and turbidity did not differ significantly (p > 0.05) between the two groups of cystic lesions. However, tiny calcifications (n = 3) and vascular flow on color Doppler US (n = 3) were noted in only neuroblastomas. The cystic neuroblastomas became complex solid and cystic masses, and did not disappear for up to 90 days in the three following cases, whereas 11 of the 14 (79%) hemorrhagic pseudocysts disappeared completely and the three remaining (27%) evolved to calcifications only. Although the imaging findings of two groups of cystic lesions were similar, prenatal detection, the presence of calcification on initial images, vascularity on color Doppler US, and evolution to a more complex mass may all favor neuroblastomas

  6. Identification of epigenetically regulated genes that predict patient outcome in neuroblastoma

    International Nuclear Information System (INIS)

    Carén, Helena; Djos, Anna; Nethander, Maria; Sjöberg, Rose-Marie; Kogner, Per; Enström, Camilla; Nilsson, Staffan; Martinsson, Tommy

    2011-01-01

    Epigenetic mechanisms such as DNA methylation and histone modifications are important regulators of gene expression and are frequently involved in silencing tumor suppressor genes. In order to identify genes that are epigenetically regulated in neuroblastoma tumors, we treated four neuroblastoma cell lines with the demethylating agent 5-Aza-2'-deoxycytidine (5-Aza-dC) either separately or in conjunction with the histone deacetylase inhibitor trichostatin A (TSA). Expression was analyzed using whole-genome expression arrays to identify genes activated by the treatment. These data were then combined with data from genome-wide DNA methylation arrays to identify candidate genes silenced in neuroblastoma due to DNA methylation. We present eight genes (KRT19, PRKCDBP, SCNN1A, POU2F2, TGFBI, COL1A2, DHRS3 and DUSP23) that are methylated in neuroblastoma, most of them not previously reported as such, some of which also distinguish between biological subsets of neuroblastoma tumors. Differential methylation was observed for the genes SCNN1A (p < 0.001), PRKCDBP (p < 0.001) and KRT19 (p < 0.01). Among these, the mRNA expression of KRT19 and PRKCDBP was significantly lower in patients that have died from the disease compared with patients with no evidence of disease (fold change -8.3, p = 0.01 for KRT19 and fold change -2.4, p = 0.04 for PRKCDBP). In our study, a low methylation frequency of SCNN1A, PRKCDBP and KRT19 is significantly associated with favorable outcome in neuroblastoma. It is likely that analysis of specific DNA methylation will be one of several methods in future patient therapy stratification protocols for treatment of childhood neuroblastomas

  7. PHOX2B reliably distinguishes neuroblastoma among small round blue cell tumours.

    Science.gov (United States)

    Hung, Yin P; Lee, John P; Bellizzi, Andrew M; Hornick, Jason L

    2017-11-01

    Neuroblastoma shows considerable histological overlap with other small round blue cell tumours. PHOX2B, a transcription factor that is essential for autonomic nervous system development, has been reported as an immunohistochemical marker for neuroblastoma. The aim of this study was to validate the specificity and diagnostic utility of PHOX2B for peripheral neuroblastic tumours. We evaluated 240 cases (133 in whole-tissue sections; 107 in tissue microarrays), including 76 peripheral neuroblastic tumours (median age 2 years; including four adults) and 164 other tumours: 44 Wilms tumours; 20 Ewing sarcomas; 10 each of CIC-rearranged round cell sarcomas, poorly differentiated synovial sarcomas, lymphoblastic lymphomas, alveolar rhabdomyosarcomas, embryonal rhabdomyosarcomas, mesenchymal chondrosarcomas, Merkel cell carcinomas, olfactory neuroblastomas, and melanomas; and five each of NUT midline carcinomas and desmoplastic small round cell tumours. Immunohistochemistry for PHOX2B was performed with a rabbit monoclonal antibody. PHOX2B positivity was defined as the presence of nuclear immunoreactivity in ≥5% of cells. PHOX2B was positive in 70 (92%) peripheral neuroblastic tumours, including 68 of 72 (94%) paediatric and two of four (50%) adult cases. Furthermore, PHOX2B was consistently negative in all non-peripheral neuroblastic tumours, with staining being absent in 160 cases and limited in four cases. PHOX2B is a highly sensitive and specific immunohistochemical marker for peripheral neuroblastic tumours, including neuroblastoma. PHOX2B reliably distinguishes neuroblastoma from histological mimics such as Wilms tumour, Ewing sarcoma, and CIC-rearranged round cell sarcoma. PHOX2B negativity in two of four adult neuroblastoma cases raises the possibility that some adult neuroblastomas are of a different lineage than paediatric cases. © 2017 John Wiley & Sons Ltd.

  8. LINC00673 rs11655237 C>T confers neuroblastoma susceptibility in Chinese population.

    Science.gov (United States)

    Zhang, Zhuorong; Chang, Yitian; Jia, Wei; Zhang, Jiao; Zhang, Ruizhong; Zhu, Jinhong; Yang, Tianyou; Xia, Huimin; Zou, Yan; He, Jing

    2018-02-28

    Neuroblastoma, which accounts for approximately 10% of all pediatric cancer-related deaths, has become a therapeutic challenge and global burden attributed to poor outcomes and mortality rates of its high-risk form. Previous genome-wide association studies (GWASs) identified the LINC00673 rs11655237 C>T polymorphism to be associated with the susceptibility of several malignant tumors. However, the association between this polymorphism and neuroblastoma susceptibility is not clear. We genotyped LINC00673 rs11655237 C>T in 393 neuroblastoma patients in comparison with 812 age-, gender-, and ethnicity-matched healthy controls. We found a significant association between the LINC00673 rs11655237 C>T polymorphism and neuroblastoma risk (TT compared with CC: adjusted odds ratio (OR) =1.80, 95% confidence interval (CI) =1.06-3.06, P =0.029; TT/CT compared with CC: adjusted OR =1.31, 95% CI =1.02-1.67, P =0.033; and T compared with C: adjusted OR =1.29, 95% CI =1.06-1.58, P =0.013). Furthermore, stratified analysis indicated that the rs11655237 T allele carriers were associated with increased neuroblastoma risk for patients with tumor originating from the adrenal gland (adjusted OR =1.51, 95% CI =1.06-2.14, P =0.021) and International Neuroblastoma Staging System (INSS) stage IV disease (adjusted OR =1.60, 95% CI =1.12-2.30, P =0.011). In conclusion, we verified that the LINC00673 rs11655237 C>T polymorphism might be associated with neuroblastoma susceptibility. Prospective studies with a large sample size and different ethnicities are needed to validate our findings. © 2018 The Author(s).

  9. MDCT assessment of resectability in hilar cholangiocarcinoma.

    Science.gov (United States)

    Ni, Qihong; Wang, Haolu; Zhang, Yunhe; Qian, Lijun; Chi, Jiachang; Liang, Xiaowen; Chen, Tao; Wang, Jian

    2017-03-01

    The purpose of this study is to investigate the value of multidetector computed tomography (MDCT) assessment of resectability in hilar cholangiocarcinoma, and to identify the factors associated with unresectability and accurate evaluation of resectability. From January 2007 to June 2015, a total of 77 consecutive patients were included. All patients had preoperative MDCT (with MPR and MinIP) and surgical treatment, and were pathologically proven with hilar cholangiocarcinoma. The MDCT images were reviewed retrospectively by two senior radiologists and one hepatobiliary surgeon. The surgical findings and pathologic results were considered to be the gold standard. The Chi square test was used to identify factors associated with unresectability and accurate evaluation of resectability. The sensitivity, specificity, and overall accuracy of MDCT assessment were 83.3 %, 75.9 %, and 80.5 %, respectively. The main causes of inaccuracy were incorrect evaluation of N2 lymph node metastasis (4/15) and distant metastasis (4/15). Bismuth type IV tumor, main or bilateral hepatic artery involvement, and main or bilateral portal vein involvement were highly associated with unresectability (P hilar cholangiocarcinoma. Bismuth type IV tumor and main or bilateral vascular involvement highly suggest the unresectability of hilar cholangiocarcinoma. Patients without biliary drainage have a more accurate MDCT evaluation of resectability. We suggest MDCT should be performed before biliary drainage to achieve an accurate evaluation of resectability in hilar cholangiocarcinoma.

  10. Vertebral Column Resection for Rigid Spinal Deformity.

    Science.gov (United States)

    Saifi, Comron; Laratta, Joseph L; Petridis, Petros; Shillingford, Jamal N; Lehman, Ronald A; Lenke, Lawrence G

    2017-05-01

    Broad narrative review. To review the evolution, operative technique, outcomes, and complications associated with posterior vertebral column resection. A literature review of posterior vertebral column resection was performed. The authors' surgical technique is outlined in detail. The authors' experience and the literature regarding vertebral column resection are discussed at length. Treatment of severe, rigid coronal and/or sagittal malalignment with posterior vertebral column resection results in approximately 50-70% correction depending on the type of deformity. Surgical site infection rates range from 2.9% to 9.7%. Transient and permanent neurologic injury rates range from 0% to 13.8% and 0% to 6.3%, respectively. Although there are significant variations in EBL throughout the literature, it can be minimized by utilizing tranexamic acid intraoperatively. The ability to correct a rigid deformity in the spine relies on osteotomies. Each osteotomy is associated with a particular magnitude of correction at a single level. Posterior vertebral column resection is the most powerful posterior osteotomy method providing a successful correction of fixed complex deformities. Despite meticulous surgical technique and precision, this robust osteotomy technique can be associated with significant morbidity even in the most experienced hands.

  11. Murine Ileocolic Bowel Resection with Primary Anastomosis

    Science.gov (United States)

    Perry, Troy; Borowiec, Anna; Dicken, Bryan; Fedorak, Richard; Madsen, Karen

    2014-01-01

    Intestinal resections are frequently required for treatment of diseases involving the gastrointestinal tract, with Crohn’s disease and colon cancer being two common examples. Despite the frequency of these procedures, a significant knowledge gap remains in describing the inherent effects of intestinal resection on host physiology and disease pathophysiology. This article provides detailed instructions for an ileocolic resection with primary end-to-end anastomosis in mice, as well as essential aspects of peri-operative care to maximize post-operative success. When followed closely, this procedure yields a 95% long-term survival rate, no failure to thrive, and minimizes post-operative complications of bowel obstruction and anastomotic leak. The technical challenges of performing the procedure in mice are a barrier to its wide spread use in research. The skills described in this article can be acquired without previous surgical experience. Once mastered, the murine ileocolic resection procedure will provide a reproducible tool for studying the effects of intestinal resection in models of human disease. PMID:25406841

  12. Resection for secondary malignancy of the pancreas.

    Science.gov (United States)

    Hung, Jui-Hsia; Wang, Shin-E; Shyr, Yi-Ming; Su, Cheng-Hsi; Chen, Tien-Hua; Wu, Chew-Wun

    2012-01-01

    This study tried to clarify the role of pancreatic resection in the treatment of secondary malignancy with metastasis or local invasion to the pancreas in terms of surgical risk and survival benefit. Data of secondary malignancy of the pancreas from our 19 patients and cases reported in the English literature were pooled together for analysis. There were 329 cases of resected secondary malignancy of the pancreas, including 241 cases of metastasis and 88 cases of local invasion. The most common primary tumor metastatic to the pancreas and amenable to resection was renal cell carcinoma (RCC) (73.9%). More than half (52.3%) of the primary cancers with local invasion to the pancreas were colon cancer, and nearly half (40.9%) were stomach cancer. The median metastatic interval was 84 months (7 years) for overall primary tumors and 108 months (9 years) for RCC. The 5-year survival for secondary malignancy of the pancreas after resection was 61.1% for metastasis and 58.9% for local invasion, with 72.8% for RCC metastasis, 69.0% for colon cancer, and 43.8% for stomach cancer with local invasion to the pancreas. Pancreatic resection should not be precluded for secondary malignancy of the pancreas because long-term survival could be achieved with acceptable surgical risk in selected patients.

  13. Modernization of the accident localisation system and relevant dose exposure on unit four of KNPP

    International Nuclear Information System (INIS)

    Valtchev, G.; Neshkova, M.; Nikilov, A.

    2005-01-01

    In 2001 a modernization of the accident localisation system (ALS) on Unit 4 was accomplished. The outage duration was longer then usually and special dose budget was elaborated. All ALS work was performed by external organisation. An ALARA implementation was recognised priority. The really accumulated collective doses were analysed and conclusions drawn. A short film on CD was prepared. (authors)

  14. How active ingredient localisation in plant tissues determines the targeted pest spectrum of different chemistries

    DEFF Research Database (Denmark)

    Buchholz, Anke; Trapp, Stefan

    2016-01-01

    information sets revealed that the intracellular localisation of active ingredients determines the performance of test compounds against different target pests because of different feeding behaviours: mites feed on mesophyll, and aphids and whiteflies mostly in the vascular system. Polar compounds have a slow...

  15. Quantitation and localisation of (in vitro) transglutaminase-catalysed glutamine hydroxylation using mass spectrometry

    NARCIS (Netherlands)

    Piersma, S.R.; Pijpekamp, A. van de; Wijngaards, G.; Gruppen, H.; Boumans, H.

    2002-01-01

    A mass spectrometric approach was chosen to quantify and localise in vitro enzymatically modified glutamine (Gln) residues in a glutamine-rich protein. This protein (named dB1), a cloned domain of the high molecular weight wheat glutenin subunit Dx5, was modified by microbial transglutaminase

  16. An efficient approach to node localisation and tracking in wireless sensor networks

    CSIR Research Space (South Africa)

    Mwila, MK

    2014-12-01

    Full Text Available and efficient localisation method that makes use of an improved RSSI distance estimation model by including the antenna radiation pattern as well as nodes orientations is presented. Mathematical models for distance estimation, cost function and gradient of cost...

  17. A machine-hearing system exploiting head movements for binaural sound localisation in reverberant conditions

    DEFF Research Database (Denmark)

    May, Tobias; Ma, Ning; Wierstorf, Hagen

    2015-01-01

    This paper is concerned with machine localisation of multiple active speech sources in reverberant environments using two (binaural) microphones. Such conditions typically present a problem for ‘classical’ binaural models. Inspired by the human ability to utilise head movements, the current study...

  18. Localised and Learnt Applications of Machine Learning for Robotic Incremental Sheet Forming

    DEFF Research Database (Denmark)

    Nicholas, Paul; Zwierzycki, Mateusz; Ramsgaard Thomsen, Mette

    2017-01-01

    Sheet Forming (ISF) and exemplified in the fabrication of a bridge structure. The methods we describe compensate for springback and improve forming tolerance by using localised in-process distance sensing to adapt tool-paths, and by using pre-process supervised machine learning to predict stringback...

  19. Immunohistochemical localisation and developmental aspects of epidermal growth factor in the rat

    DEFF Research Database (Denmark)

    Raaberg, L; Nexø, E; Damsgaard Mikkelsen, J

    1988-01-01

    The tissue localisation and time of first appearance of Epidermal Growth Factor (EGF) in the developing rat were investigated by means of immunohistochemistry, radioimmunoassay and radioreceptor assay. In this study we were able to show, that EGF appears prenatally in the lung and the kidney from...

  20. Mozart's African jacket: Die Zauberflöte and its localisation in The ...

    African Journals Online (AJOL)

    , the change in time, space, context and symbolism in a localised or indigenised South African version of Mozart's Die Zauberflöte, K. 620. It addresses the lacunae between desiderata expressed in the White Paper on Arts, Culture and ...

  1. Exploiting deep neural networks and head movements for binaural localisation of multiple speakers in reverberant conditions

    DEFF Research Database (Denmark)

    Ma, Ning; Brown, Guy J.; May, Tobias

    2015-01-01

    This paper presents a novel machine-hearing system that exploits deep neural networks (DNNs) and head movements for binaural localisation of multiple speakers in reverberant conditions. DNNs are used to map binaural features, consisting of the complete crosscorrelation function (CCF) and interaural...

  2. Globalisation and Localisation in Music Education in Hong Kong and Taiwan

    Science.gov (United States)

    Ho, Wai-Chung

    2013-01-01

    The purpose of the study is to analyse and discuss the influences of globalisation and localisation on music education in Hong Kong and Taiwan. It argues that the reform of music education concerns changes to the contents of the curriculum that envisage the cultural and political developments that arise from processes of globalisation and…

  3. Tumour Suppressor Adenomatous Polyposis Coli (APC) localisation is regulated by both Kinesin-1 and Kinesin-2

    NARCIS (Netherlands)

    Ruane, Peter T; Gumy, Laura F; Bola, Becky; Anderson, Beverley; Wozniak, Marcin J; Hoogenraad, Casper C; Allan, Victoria J

    2016-01-01

    Microtubules and their associated proteins (MAPs) underpin the polarity of specialised cells. Adenomatous polyposis coli (APC) is one such MAP with a multifunctional agenda that requires precise intracellular localisations. Although APC has been found to associate with kinesin-2 subfamily members,

  4. Localisation of the neuropeptide PACAP and its receptors in the rat parathyroid and thyroid glands

    DEFF Research Database (Denmark)

    Fahrenkrug, Jan; Hannibal, Jens

    2011-01-01

    PACAP (pituitary adenylate cyclase activating polypeptide) is widely distributed neuropeptide acting via three subtypes of receptors, PAC(1), VPAC(1) and VPAC(2). Here we examined the localisation and nature of PACAP-immunoreactive nerves in the rat thyroid and parathyroid glands and defined the ...

  5. Diagnosis and localisation of insulinoma: the value of modern magnetic resonance imaging in conjunction with calcium stimulation catheterisation.

    Science.gov (United States)

    Druce, Maralyn R; Muthuppalaniappan, Vasantha M; O'Leary, Benjamin; Chew, Shern L; Drake, William M; Monson, John P; Akker, Scott A; Besser, Michael; Sahdev, Anju; Rockall, Andrea; Vyas, Soumil; Bhattacharya, Satya; Matson, Matthew; Berney, Daniel; Reznek, R H; Grossman, Ashley B

    2010-05-01

    Preoperative localisation of insulinoma improves cure rate and reduces complications, but may be challenging. To review diagnostic features and localisation accuracy for insulinomas. Cross-sectional, retrospective analysis. A single tertiary referral centre. Patients with insulinoma in the years 1990-2009, including sporadic tumours and those in patients with multiple endocrine neoplasia syndromes. Patients were identified from a database, and case notes and investigation results were reviewed. Tumour localisation by computed tomography (CT), magnetic resonance imaging (MRI), octreotide scanning, endoscopic ultrasound (EUS) and calcium stimulation was evaluated. Insulinoma localisation was compared to histologically confirmed location following surgical excision. Thirty-seven instances of biochemically and/or histologically proven insulinoma were identified in 36 patients, of which seven were managed medically. Of the 30 treated surgically, 25 had CT (83.3%) and 28 had MRI (90.3%), with successful localisation in 16 (64%) by CT and 21 (75%) by MRI respectively. Considered together, such imaging correctly localised 80% of lesions. Radiolabelled octreotide scanning was positive in 10 out of 20 cases (50%); EUS correctly identified 17 lesions in 26 patients (65.4%). Twenty-seven patients had calcium stimulation testing, of which 6 (22%) did not localise, 17 (63%) were correctly localised, and 4 (15%) gave discordant or confusing results. Preoperative localisation of insulinomas remains challenging. A pragmatic combination of CT and especially MRI predicts tumour localisation with high accuracy. Radionuclide imaging and EUS were less helpful but may be valuable in selected cases. Calcium stimulation currently remains useful in providing an additional functional perspective.

  6. Neurologic deficit after resection of the sacrum.

    Science.gov (United States)

    Biagini, R; Ruggieri, P; Mercuri, M; Capanna, R; Briccoli, A; Perin, S; Orsini, U; Demitri, S; Arlecchini, S

    1997-01-01

    The authors describe neurologic deficit (sensory, motor, and sphincteral) resulting from sacrifice of the sacral nerve roots removed during resection of the sacrum. The anatomical and functional bases of sphincteral continence and the amount of neurologic deficit are discussed based on level of sacral resection. A large review of the literature on the subject is reported and discussed. The authors emphasize how the neurophysiological bases of sphincteral continence (rectum and bladder) and of sexual ability are still not well known, and how the literature reveals disagreement on the subject. A score system is proposed to evaluate neurologic deficit. The clinical model of neurologic deficit caused by resection of the sacrum may be extended to an evaluation of post-traumatic deficit.

  7. Scintigraphy by sup 99m Tc-in vivo labeled red blood cells. Detection of gastrointestinal bleeding following duodenum-preserving resection of the head of the pancreas. Die Szintigraphie mit sup 99m Tc-in-vivo-markierten Erythrozyten. Nachweis einer intestinalen Blutung nach duodenumerhaltender Pankreaskopfresektion

    Energy Technology Data Exchange (ETDEWEB)

    Brecht-Krauss, D. (Ulm Univ. (Germany, F.R.). Abt. Nuklearmedizin); Schnarkowski, P.; Friedrich, J.M. (Ulm Univ. (Germany, F.R.). Abt. Roentgendiagnostik)

    1990-09-01

    Following resection of the head of the pancreas while preserving the duodenum a gastrointestinal haemorrhage was localised by red blood cells labeled in vivo with technetium-99m. The previously performed endoscopy and angiography were normal. The haemorrhage in the region of the pancreaticojejunal anastomosis was confirmed intraoperatively. If intermittent bleedings are suspected, scintigraphy should be performed as a routine measure besides endoscopy and angiography. (orig.).

  8. Robotic versus laparoscopic resection of liver tumours

    Science.gov (United States)

    Berber, Eren; Akyildiz, Hizir Yakup; Aucejo, Federico; Gunasekaran, Ganesh; Chalikonda, Sricharan; Fung, John

    2010-01-01

    Background There are scant data in the literature regarding the role of robotic liver surgery. The aim of the present study was to develop techniques for robotic liver tumour resection and to draw a comparison with laparoscopic resection. Methods Over a 1-year period, nine patients underwent robotic resection of peripherally located malignant lesions measuring <5 cm. These patients were compared prospectively with 23 patients who underwent laparoscopic resection of similar tumours at the same institution. Statistical analyses were performed using Student's t-test, χ2-test and Kaplan–Meier survival. All data are expressed as mean ± SEM. Results The groups were similar with regards to age, gender and tumour type (P = NS). Tumour size was similar in both groups (robotic −3.2 ± 1.3 cm vs. laparoscopic −2.9 ± 1.3 cm, P = 0.6). Skin-to-skin operative time was 259 ± 28 min in the robotic vs. 234 ± 17 min in the laparoscopic group (P = 0.4). There was no difference between the two groups regarding estimated blood loss (EBL) and resection margin status. Conversion to an open operation was only necessary in one patient in the robotic group. Complications were observed in one patient in the robotic and four patients in the laparoscopic groups. The patients were followed up for a mean of 14 months and disease-free survival (DFS) was equivalent in both groups (P = 0.6). Conclusion The results of this initial study suggest that, for selected liver lesions, a robotic approach provides similar peri-operative outcomes compared with laparoscopic liver resection (LLR). PMID:20887327

  9. Hepatic resection and regeneration. Past and present

    International Nuclear Information System (INIS)

    Hatsuse, Kazuo

    2007-01-01

    Hepatic surgery has been performed on condition that the liver regenerates after hepatic resection, and the development of liver anatomy due to Glisson, Rex, and Couinaud has thrown light on hepatic surgery Understanding of feeding and drainage vessels became feasible for systemic hepatic resection; however, it seems to have been the most important problem to control the bleeding during hepatic resection. New types of devices such as cavitron ultrasonic surgical aspirator (CUSA) and Microwave coagulation were exploited to control blood loss during hepatic surgery. Pringle maneuver for exclusion feeding vessels of the liver and the decrease of central venous pressure during anesthesia enabled further decrease of blood loss. Nowadays, 3D-CT imaging may depict feeding and drainage vessels in relation to liver mass, and surgeons can simulate hepatic surgery in virtual reality before surgery, allowing hepatectomy to be performed without blood transfusion. Thus, hepatic resection has been a safe procedure, but there's been a significant research on how much of the liver can be resected without hepatic failure. A prediction scoring system based on ICGR15, resection rates, and age is mostly reliable in some criteria. Even if hepatectomy is performed with a good prediction score, the massive bleeding and associated infection may induce postoperative hepatic failure, while the criteria of postoperative hepatic failure have not yet established. Hepatic failure is supposed to be induced by the apoptosis of mature hepatocytes and necrosis originated from microcirculation disturbance of the liver. Prostaglandin E1 for the improvement of microcirculation, steroid for the inhibition of cytokines inducing apoptosis, and blood purification to exclude cytokines have been tried separately or concomitantly. New therapeutic approaches, especially hepatic regeneration from the stem cell, are expected. (author)

  10. Allelic loss of the short arm of chromosome 4 in neuroblastoma suggests a novel tumour suppressor gene locus

    NARCIS (Netherlands)

    Caron, H.; van Sluis, P.; Buschman, R.; Pereira do Tanque, R.; Maes, P.; Beks, L.; de Kraker, J.; Voûte, P. A.; Vergnaud, G.; Westerveld, A.; Slater, R.; Versteeg, R.

    1996-01-01

    Neuroblastoma is a childhood neural crest tumour, genetically characterized by frequent deletions of the short arm of chromosome 1 and amplification of N-myc. Here we report the first evidence for a neuroblastoma tumour suppressor locus on 4pter. Cytogenetically we demonstrated rearrangements of 4p

  11. Protein tyrosine phosphatase receptor delta acts as a neuroblastoma tumor suppressor by destabilizing the aurora kinase a oncogene

    LENUS (Irish Health Repository)

    Meehan, Maria

    2012-02-05

    Abstract Background Protein tyrosine phosphatase receptor delta (PTPRD) is a member of a large family of protein tyrosine phosphatases which negatively regulate tyrosine phosphorylation. Neuroblastoma is a major childhood cancer arising from precursor cells of the sympathetic nervous system which is known to acquire deletions and alterations in the expression patterns of PTPRD, indicating a potential tumor suppressor function for this gene. The molecular mechanism, however, by which PTPRD renders a tumor suppressor effect in neuroblastoma is unknown. Results As a molecular mechanism, we demonstrate that PTPRD interacts with aurora kinase A (AURKA), an oncogenic protein that is over-expressed in multiple forms of cancer, including neuroblastoma. Ectopic up-regulation of PTPRD in neuroblastoma dephosphorylates tyrosine residues in AURKA resulting in a destabilization of this protein culminating in interfering with one of AURKA\\'s primary functions in neuroblastoma, the stabilization of MYCN protein, the gene of which is amplified in approximately 25 to 30% of high risk neuroblastoma. Conclusions PTPRD has a tumor suppressor function in neuroblastoma through AURKA dephosphorylation and destabilization and a downstream destabilization of MYCN protein, representing a novel mechanism for the function of PTPRD in neuroblastoma.

  12. Galectin-3 impairment of MYCN-dependent apoptosis-sensitive phenotype is antagonized by nutlin-3 in neuroblastoma cells.

    Directory of Open Access Journals (Sweden)

    Veronica Veschi

    Full Text Available MYCN amplification occurs in about 20-25% of human neuroblastomas and characterizes the majority of the high-risk cases, which display less than 50% prolonged survival rate despite intense multimodal treatment. Somehow paradoxically, MYCN also sensitizes neuroblastoma cells to apoptosis, understanding the molecular mechanisms of which might be relevant for the therapy of MYCN amplified neuroblastoma. We recently reported that the apoptosis-sensitive phenotype induced by MYCN is linked to stabilization of p53 and its proapoptotic kinase HIPK2. In MYCN primed neuroblastoma cells, further activation of both HIPK2 and p53 by Nutlin-3 leads to massive apoptosis in vitro and to tumor shrinkage and impairment of metastasis in xenograft models. Here we report that Galectin-3 impairs MYCN-primed and HIPK2-p53-dependent apoptosis in neuroblastoma cells. Galectin-3 is broadly expressed in human neuroblastoma cell lines and tumors and is repressed by MYCN to induce the apoptosis-sensitive phenotype. Despite its reduced levels, Galectin-3 can still exert residual antiapoptotic effects in MYCN amplified neuroblastoma cells, possibly due to its specific subcellular localization. Importantly, Nutlin-3 represses Galectin-3 expression, and this is required for its potent cell killing effect on MYCN amplified cell lines. Our data further characterize the apoptosis-sensitive phenotype induced by MYCN, expand our understanding of the activity of MDM2-p53 antagonists and highlight Galectin-3 as a potential biomarker for the tailored p53 reactivation therapy in patients with high-risk neuroblastomas.

  13. Genome‐wide DNA methylation analysis identifies MEGF10 as a novel epigenetically repressed candidate tumor suppressor gene in neuroblastoma

    Science.gov (United States)

    Charlet, Jessica; Tomari, Ayumi; Dallosso, Anthony R.; Szemes, Marianna; Kaselova, Martina; Curry, Thomas J.; Almutairi, Bader; Etchevers, Heather C.; McConville, Carmel; Malik, Karim T. A.

    2016-01-01

    Neuroblastoma is a childhood cancer in which many children still have poor outcomes, emphasising the need to better understand its pathogenesis. Despite recent genome‐wide mutation analyses, many primary neuroblastomas do not contain recognizable driver mutations, implicating alternate molecular pathologies such as epigenetic alterations. To discover genes that become epigenetically deregulated during neuroblastoma tumorigenesis, we took the novel approach of comparing neuroblastomas to neural crest precursor cells, using genome‐wide DNA methylation analysis. We identified 93 genes that were significantly differentially methylated of which 26 (28%) were hypermethylated and 67 (72%) were hypomethylated. Concentrating on hypermethylated genes to identify candidate tumor suppressor loci, we found the cell engulfment and adhesion factor gene MEGF10 to be epigenetically repressed by DNA hypermethylation or by H3K27/K9 methylation in neuroblastoma cell lines. MEGF10 showed significantly down‐regulated expression in neuroblastoma tumor samples; furthermore patients with the lowest‐expressing tumors had reduced relapse‐free survival. Our functional studies showed that knock‐down of MEGF10 expression in neuroblastoma cell lines promoted cell growth, consistent with MEGF10 acting as a clinically relevant, epigenetically deregulated neuroblastoma tumor suppressor gene. © 2016 The Authors. Molecular Carcinogenesis Published by Wiley Periodicals, Inc. PMID:27862318

  14. FOXO3a is a major target of inactivation by PI3K/AKT signaling in aggressive neuroblastoma

    NARCIS (Netherlands)

    Santo, Evan E.; Stroeken, Peter; Sluis, Peter V.; Koster, Jan; Versteeg, Rogier; Westerhout, Ellen M.

    2013-01-01

    Neuroblastoma is a pediatric tumor of the peripheral sympathetic nervous system with a highly variable prognosis. Activation of the phosphoinositide 3-kinase (PI3K)/AKT pathway in neuroblastoma is correlated with poor patient prognosis, but the precise downstream effectors mediating this effect have

  15. Needle aspiration biopsy in the diagnosis of lytic bone lesions in histiocytosis X, Ewing's sarcoma and neuroblastoma

    International Nuclear Information System (INIS)

    Thommesen, P.; Frederiksen, P.; Loewhagen, T.; Willems, J.S.

    1978-01-01

    Cytologic smears obtained by needle aspiration biopsy of lytic bone lesions in 15 patients with histiocytosis X, Ewing's sarcoma and neuroblastoma were reviewed. After conventional staining, histiocytosis X could be diagnosed and differentiated from small cell tumours such as Ewing's sarcoma and neuroblastoma. The need for sampling material for cytochemical and ultrastructural analysis of these small cell tumours by needle aspiration is emphasized. (Auth.)

  16. Dual targeting of MDM2 and BCL2 as a therapeutic strategy in neuroblastoma.

    Science.gov (United States)

    Van Goethem, Alan; Yigit, Nurten; Moreno-Smith, Myrthala; Vasudevan, Sanjeev A; Barbieri, Eveline; Speleman, Frank; Shohet, Jason; Vandesompele, Jo; Van Maerken, Tom

    2017-08-22

    Wild-type p53 tumor suppressor activity in neuroblastoma tumors is hampered by increased MDM2 activity, making selective MDM2 antagonists an attractive therapeutic strategy for this childhood malignancy. Since monotherapy in cancer is generally not providing long-lasting clinical responses, we here aimed to identify small molecule drugs that synergize with idasanutlin (RG7388). To this purpose we evaluated 15 targeted drugs in combination with idasanutlin in three p53 wild type neuroblastoma cell lines and identified the BCL2 inhibitor venetoclax (ABT-199) as a promising interaction partner. The venetoclax/idasanutlin combination was consistently found to be highly synergistic in a diverse panel of neuroblastoma cell lines, including cells with high MCL1 expression levels. A more pronounced induction of apoptosis was found to underlie the synergistic interaction, as evidenced by caspase-3/7 and cleaved PARP measurements. Mice carrying orthotopic xenografts of neuroblastoma cells treated with both idasanutlin and venetoclax had drastically lower tumor weights than mice treated with either treatment alone. In conclusion, these data strongly support the further evaluation of dual BCL2/MDM2 targeting as a therapeutic strategy in neuroblastoma.

  17. Expression of Truncated Neurokinin-1 Receptor in Childhood Neuroblastoma is Independent of Tumor Biology and Stage.

    Science.gov (United States)

    Pohl, Alexandra; Kappler, Roland; Mühling, Jakob; VON Schweinitz, Dietrich; Berger, Michael

    2017-11-01

    Neuroblastoma is an embryonal malignancy arising from the aberrant growth of neural crest progenitor cells of the sympathetic nervous system. The tachykinin receptor 1 (TACR1) - substance P complex is associated with tumoral angiogenesis and cell proliferation in a variety of cancer types. Inhibition of TACR1 was recently described to impede growth of NB cell lines. However, the relevance of TACR1 in clinical settings is unknown. We investigated gene expression levels of full-length and truncated TACR1 in 59 neuroblastomas and correlated these data with the patients' clinical parameters such as outcome, metastasis, International Neuroblastoma Staging System (INSS) status, MYCN proto-oncogene, bHLH transcription factor (MYCN) status, gender and age. Our results indicated that TACR1 is ubiquitously expressed in neuroblastoma but expression levels are independent of clinical parameters. Our data suggest that TACR1 might serve as a potent anticancer target in a large variety of patients with neuroblastoma, independent of tumor biology and clinical stage. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  18. The value of anterior displacement of the abdominal aorta in diagnosing neuroblastoma in children

    Energy Technology Data Exchange (ETDEWEB)

    Schiavon, Jose Luiz de Oliveira; Caran, Eliana Maria Monteiro; Lederman, Henrique Manoel, E-mail: schiavon00@gmail.com [Universidade Federal de Sao Paulo (EPM/UNIFESP), Sao Paulo, SP (Brazil). Escola Paulista de Medicina; Odone Filho, Vicente [Universidade de Sao Paulo (FM/USP), Sao Paulo, SP (Brazil). Faculdade de Medicina

    2016-11-15

    Objective: To determine the value of anterior displacement of the abdominal aorta, when present at any level or only at the level of the adrenal gland, contralateral to the mass, in diagnosing neuroblastoma on computed tomography or magnetic resonance imaging in children up to 7 years of age. Materials and Methods: Imaging examinations of 66 patients were classified by consensus as for the presence of anterior aorta displacement and were compared with the pathology report. Results: We found anterior abdominal aorta displacement in 26 (39.39%) of the 66 patients evaluated. Among those 26 patients, we identified neuroblastoma in 22 (84.62%), nephroblastoma in 3 (11.54%), and Burkitt lymphoma in 1 (3.85%). The positive predictive value was 84.62%, and the specificity was 88.24%. The displacement of the aorta was at the adrenal level, contralateral to the mass, in 14 cases, all of which were attributed to neuroblastoma. Conclusion: When the abdominal aorta is displaced at the level of the adrenal gland, contralateral to the mass, it can be said that the diagnosis is neuroblastoma, whereas abdominal aorta displacement occurring at other abdominal levels has a positive predictive value for neuroblastoma of approximately 85%. (author)

  19. Variability in surface antigen expression on neuroblastoma cells as revealed by monoclonal antibodies

    International Nuclear Information System (INIS)

    Malpas, J.S.; Kemshead, J.T.; Pritchard, J.; Greaves, M.F.

    1982-01-01

    In treatment programmes for neuroblastoma involving autologous bone marrow transplantation, a problem exists in the identification of small numbers of metastatic tumour cells present in the marrow aspirates. Reinfusion of tumour cells along with normal bone marrow may reseed the tumour within a patient who has received high dose chemotherapy. Formalin-induced fluorescence in neuroblastoma is a possible diagnostic aid, but this method has no therapeutic potential. Other methods of detecting tumour relying on gross physiological changes in the patient are not suitable for diagnosis of minimal metastatic disease. As an immunological approach to the problem, rabbit antisera to neuroblastoma have been raised but these reagents suffer from low titre after absorption to make them specific. The authors have used the technique of somatic cell hybridisation to raise monoclonal antibodies which bind to neuroblastoma cells and not to normal haemopoietic progenitors. A panel of such reagents to demonstrate heterogeneity in antigen expression amongst metastatic neuroblastoma cells was employed in a radioimmunoassay as diagnostic aid for this problem. (Auth.)

  20. Neuroblastoma originating from soft tissue at the crus and its radiological feature

    International Nuclear Information System (INIS)

    Hirota, Shozo; Hanaguri, Katsuro; Hase, Mamoru; Sako, Masao.

    1984-01-01

    A very rare case of neuroblastoma originated from soft tissue at the crus in an adult man was reported especially about its radiological feature. Plain X-ray film of the leg showed slight distension of the distance between the tibia and fibula at the proximal portion of the crus. Bone scintigram using sup(99m)Tc-MDP revealed abnormal accumulation at the right upper crus. CT showed a low density mass with smooth margin being at the right upper crus. In femoral angiography, irregular arterial encasement, hypervascular fine tumor vessels, inhomogeneous tumor stain and venous obstruction were shown. Radiological findings made sure the mass to be a primary malignant soft tissue tumor at the right upper crus. Operative finding corroborated the mass to be a malignant one and the tumor extent to correspond to the angiographic diagnosis. The mass was microscopically diagnosed as neuroblastoma. It has been noted that neuroblastoma in childhood had shown extraosseous accumulation of bone seeking agent in a high frequency. Even if in an adult patient, extraosseous accumulation of bone seeking agent in soft tissue tumor, shown in this case, would suggest a mass to be indicative of neuroblastoma. Angiographically, neuroblastoma was said not to show a constant pattern. In the presented case, angiography was very significant in diagnosis of malignancy and tumor extent. (author)

  1. Meta-iodobenzylguanidine scintigraphy in neuroblastoma--a comparison with conventional X-ray and ultrasound

    International Nuclear Information System (INIS)

    Mueller-Gaertner, H.W.Er.; Erttmann, R.; Helmke, K.

    1986-01-01

    To evaluate the accuracy of meta-iodobenzylguanidine (MIBG) imaging in comparison with bone X-ray and ultrasound, 15 patients with histologically verified neuroblastoma were investigated using 123- or 131MIBG scintigraphy. 123MIBG and 131MIBG are used as the abbreviations for 123-iodine-labeled-MIBG and 131-iodine-labeled-MIBG, respectively. Either 7.4 MBq 131MIBG (n = 4) or 111-185 MBq 123MIBG (n = 11) was applied, and scans were performed 24 and 48 h PI. Anatomical orientation was provided in selected cases by single-photon emission CT or scintigraphy of other organs. X-ray procedures or ultrasound depicted 27 neuroblastoma manifestations (primary tumors and metastatic deposits); 24 of these (89%) were identified by MIBG scintigraphy. Of 42 primary neuroblastomas and metastatic deposits, 27 (64%) were detected by corresponding bone X-ray or ultrasound. The 15 neuroblastoma lesions depicted solely by MIBG scans were mainly (80%) situated in the skeletal system. Because of the pronounced physiological MIBG uptake by liver tissue, detection of intrahepatic or perihepatic tumor involvement is difficult. MIBG scintigraphy is a safe and noninvasive means of locating a wide range of neuroblastoma lesions. Its main diagnostic advantage in comparison with bone X-ray lies in the detection of bone marrow infiltration

  2. The value of anterior displacement of the abdominal aorta in diagnosing neuroblastoma in children

    International Nuclear Information System (INIS)

    Schiavon, Jose Luiz de Oliveira; Caran, Eliana Maria Monteiro; Lederman, Henrique Manoel; Odone Filho, Vicente

    2016-01-01

    Objective: To determine the value of anterior displacement of the abdominal aorta, when present at any level or only at the level of the adrenal gland, contralateral to the mass, in diagnosing neuroblastoma on computed tomography or magnetic resonance imaging in children up to 7 years of age. Materials and Methods: Imaging examinations of 66 patients were classified by consensus as for the presence of anterior aorta displacement and were compared with the pathology report. Results: We found anterior abdominal aorta displacement in 26 (39.39%) of the 66 patients evaluated. Among those 26 patients, we identified neuroblastoma in 22 (84.62%), nephroblastoma in 3 (11.54%), and Burkitt lymphoma in 1 (3.85%). The positive predictive value was 84.62%, and the specificity was 88.24%. The displacement of the aorta was at the adrenal level, contralateral to the mass, in 14 cases, all of which were attributed to neuroblastoma. Conclusion: When the abdominal aorta is displaced at the level of the adrenal gland, contralateral to the mass, it can be said that the diagnosis is neuroblastoma, whereas abdominal aorta displacement occurring at other abdominal levels has a positive predictive value for neuroblastoma of approximately 85%. (author)

  3. Comparative study between 131I-MIBG scintigraphy and other tumor markers in diagnosis of neuroblastoma

    International Nuclear Information System (INIS)

    Ohsawa, Yoshihiro; Iwafuchi, Makoto; Odano, Ikuo; Yamagiwa, Iwao.

    1989-01-01

    In order to prove the clinical usefulness in diagnosis of neuroblastoma, comparative studies between iodine-131 metaiodobenzylguanidine ( 131 I-MIBG) scintigraphy and other related tumor markers were attempted. Sixteen children diagnosed as having a neuroblastoma in recent 2 years were examined. In 5 postoperative patients in complete remission, who were negative to other tumor markers, showed no pathological accumulation of 131 I-MIBG (specificity 100%). In other 11 patients with remains of neuroblastoma, 131 I-MIBG was negative only in 2 patients (sensitivity 82%) and these 2 patients showed negative urinary excretion of catecholamine metabolites (VMA). (Negative urinary VMA was proved in 3 of 11 patients). Serum neuron-specific enolase (NSE) was elevated in all 8 preoperative patients, but only in 2 of 11 postoperative patients. On the other hand 131 I-MIBG was positive in 9 among these 11 postoperative patients in whom neuroblastoma remained. Similar relationship was obtained between 131 I-MIBG scintigraphy and serum LDH. On the basis of our present experience, we like to regard 131 I-MIBG scintigraphy as one of the most sensitive parameters for neuroblastoma during a follow-up period after treatment. (author)

  4. MAX to MYCN intracellular ratio drives the aggressive phenotype and clinical outcome of high risk neuroblastoma.

    Science.gov (United States)

    Ferrucci, Francesca; Ciaccio, Roberto; Monticelli, Sara; Pigini, Paolo; di Giacomo, Simone; Purgato, Stefania; Erriquez, Daniela; Bernardoni, Roberto; Norris, Murray; Haber, Michelle; Milazzo, Giorgio; Perini, Giovanni

    2018-03-01

    Childhood neuroblastoma, a disease of the sympathetic nervous system, is the most common solid tumour of infancy, remarkably refractory to therapeutic treatments. One of the most powerful independent prognostic indicators for this disease is the amplification of the MYCN oncogene, which occurs at high levels in approximately 25% of neuroblastomas. Interestingly, amplification and not just expression of MYCN has a strong prognostic value, although this fact appears quite surprising as MYCN is a transcription factor that requires dimerising with its partner MAX, to exert its function. This observation greatly suggests that the role of MYCN in neuroblastoma should be examined in the context of MAX expression. In this report, we show that, in contrast to what is found in normal cells, MAX expression is significantly different among primary NBs, and that its level appears to correlate with the clinical outcome of the disease. Importantly, controlled modulation of MAX expression in neuroblastoma cells with different extents of MYCN amplification, demonstrates that MAX can instruct gene transcription programs that either reinforce or weaken the oncogenic process enacted by MYCN. In general, our work illustrates that it is the MAX to MYCN ratio that can account for tumour progression and clinical outcome in neuroblastoma and proposes that such a ratio should be considered as an important criterion to the design and development of anti-MYCN therapies. Copyright © 2018 Elsevier B.V. All rights reserved.

  5. Transcription instability in high-risk neuroblastoma is associated with a global perturbation of chromatin domains.

    Science.gov (United States)

    Zanon, Carlo; Tonini, Gian Paolo

    2017-11-01

    Chromosome instability has a pivotal role among the hallmarks of cancer, but its transcriptional counterpart is rarely considered a relevant factor in cell destabilization. To examine transcription instability (TIN), we first devised a metric we named TIN index and used it to evaluate TIN on a dataset containing more than 500 neuroblastoma samples. We found that metastatic tumors from high-risk (HR) patients are characterized by significantly different TIN index values compared to low/intermediate-risk patients. Our results indicate that the TIN index is a good predictor of neuroblastoma patient's outcome, and a related TIN index gene signature (TIN-signature) is also able to predict the neuroblastoma patient's outcome with high confidence. Interestingly, we find that TIN-signature genes have a strong positional association with superenhancers in neuroblastoma tumors. Finally, we show that TIN is linked to chromatin structural domains and interferes with their integrity in HR neuroblastoma patients. This novel approach to gene expression analysis broadens the perspective of genome instability investigations to include functional aspects. © 2017 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.

  6. Suberoylanilide hydroxamic acid sensitizes neuroblastoma to paclitaxel by inhibiting thioredoxin-related protein 14-mediated autophagy.

    Science.gov (United States)

    Zhen, Zijun; Yang, Kaibin; Ye, Litong; You, Zhiyao; Chen, Rirong; Liu, Ying; He, Youjian

    2017-07-01

    Paclitaxel is not as effective for neuroblastoma as most of the front-line chemotherapeutics due to drug resistance. This study explored the regulatory mechanism of paclitaxel-associated autophagy and potential solutions to paclitaxel resistance in neuroblastoma. The formation of autophagic vesicles was detected by scanning transmission electron microscopy and flow cytometry. The autophagy-associated proteins were assessed by western blot. Autophagy was induced and the autophagy-associated proteins LC3-I, LC3-II, Beclin 1, and thioredoxin-related protein 14 (TRP14), were found to be upregulated in neuroblastoma cells that were exposed to paclitaxel. The inhibition of Beclin 1 or TRP14 by siRNA increased the sensitivity of the tumor cells to paclitaxel. In addition, Beclin 1-mediated autophagy was regulated by TRP14. Furthermore, the TRP14 inhibitor suberoylanilide hydroxamic acid (SAHA) downregulated paclitaxel-induced autophagy and enhanced the anticancer effects of paclitaxel in normal control cancer cells but not in cells with upregulated Beclin 1 and TRP14 expression. Our findings showed that paclitaxel-induced autophagy in neuroblastoma cells was regulated by TRP14 and that SAHA could sensitize neuroblastoma cells to paclitaxel by specifically inhibiting TRP14. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  7. Clinical experience with radiation enhancement by hyperbaric oxygen in children with recurrent neuroblastoma stage IV

    International Nuclear Information System (INIS)

    Voute, P.A.; Kleij, A.J. van der; De Kraker, J.; Hoefnagel, C.A.; Tiel-van Buul, M.M.C.; Gennip, H. van

    1995-01-01

    The high risk group of patients with neuroblastoma are children over 1 year with stage IV disease. Most series report a maximum of 20% survival at 5 years. For recurrent neuroblastoma stage IV, cure rates are not reported in the literature, but they are nil. Any treatment for recurrent neuroblastoma stage IV remains a therapeutic dilemma. The outcome of radiation therapy is variable. A very important factor in tumour treatment remains tumour hypoxia, and others, such as metabolic factors, also play a role. Combined application of radiation modifiers may influence the final survival rate. In an attempt to improve the survival of recurrent neuroblastoma stage IV, hyperbaric oxygen and radioionated meta-Iodobenzylguanidine (MIBG) was used in a clinical setting. Although survival may not be used as a determinant of the usefulness of a treatment for stage IV neuroblastoma disease, a better one is not available. In this study, at 28 months, a cumulative probability of survival of 32% was recorded for patients treated with [ 131 I]MIBG and hyperbaric oxygen compared to 12% for [ 131 I]MIBG treatment alone. These preliminary results are promising but further studies are needed to reveal substantial therapeutic gain. (Author)

  8. The Role of Intracellular Calcium for the Development and Treatment of Neuroblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Satheesh, Noothan Jyothi; Büsselberg, Dietrich, E-mail: dib2015@qatar-med.cornell.edu [Weill Cornell Medical College in Qatar, Qatar Foundation-Education City, POB 24144, Doha (Qatar)

    2015-05-22

    Neuroblastoma is the second most common paediatric cancer. It develops from undifferentiated simpatico-adrenal lineage cells and is mostly sporadic; however, the aetiology behind the development of neuroblastoma is still not fully understood. Intracellular calcium ([Ca{sup 2+}]{sub i}) is a secondary messenger which regulates numerous cellular processes and, therefore, its concentration is tightly regulated. This review focuses on the role of [Ca{sup 2+}]{sub i} in differentiation, apoptosis and proliferation in neuroblastoma. It describes the mechanisms by which [Ca{sup 2+}]{sub i} is regulated and how it modulates intracellular pathways. Furthermore, the importance of [Ca{sup 2+}]{sub i} for the function of anti-cancer drugs is illuminated in this review as [Ca{sup 2+}]{sub i} could be a target to improve the outcome of anti-cancer treatment in neuroblastoma. Overall, modulations of [Ca{sup 2+}]{sub i} could be a key target to induce apoptosis in cancer cells leading to a more efficient and effective treatment of neuroblastoma.

  9. Knife-assisted snare resection: a novel technique for resection of scarred polyps in the colon.

    Science.gov (United States)

    Chedgy, Fergus J Q; Bhattacharyya, Rupam; Kandiah, Kesavan; Longcroft-Wheaton, Gaius; Bhandari, Pradeep

    2016-03-01

    There have been significant advances in the management of complex colorectal polyps. Previous failed resection or polyp recurrence is associated with significant fibrosis, making endoscopic resection extremely challenging; the traditional approach to these lesions is surgery. The aim of this study was to evaluate the efficacy of a novel, knife-assisted snare resection (KAR) technique in the resection of scarred colonic polyps. This was a prospective cohort study of patients, in whom the KAR technique was used to resect scarred colonic polyps > 2  cm in size. Patients had previously undergone endoscopic mucosal resection (EMR) and developed recurrence, or EMR had been attempted but was aborted as a result of technical difficulty. A total of 42 patients underwent KAR of large (median 40  mm) scarred polyps. Surgery for benign disease was avoided in 38 of 41 patients (93 %). No life-threatening complications occurred. Recurrence was seen in six patients (16 %), five of whom underwent further endoscopic resection. The overall cure rate for KAR in complex scarred colonic polyps was 90 %. KAR of scarred colonic polyps by an expert endoscopist was an effective and safe technique with low recurrence rates. © Georg Thieme Verlag KG Stuttgart · New York.

  10. [Laparoscopic resection of stomach in case of stomach ulcer].

    Science.gov (United States)

    Sazhin, I V; Sazhin, V P; Nuzhdikhin, A V

    2014-01-01

    Laparoscopic resection of stomach was done in 84 patients with complicated peptic ulcer of stomach and duodenum. There were 1.2% post-operative complications in case of laparoscopic resection of stomach in comparison with open resection, which had 33.3% complications. There were not deaths in case of laparoscopic resection of stomach. This indication was about 4% in patients after open resection. It was determined that functionalefficiency afterlaparoscopic resection was in 1.6-1.8 times higher than afteropen resectionof stomach.

  11. Metastatic neuroblastoma presenting as refusal to use the left upper extremity in a six-year-old girl

    Directory of Open Access Journals (Sweden)

    Casey Grover

    2014-12-01

    Full Text Available Neuroblastoma is the most common extracranial neoplasm in children, commonly presenting at an advanced stage. Despite the high prevalence of metastatic disease with neuroblastoma, metastases to the central nervous system are rare and predominantly involve the spinal cord. We present a case of neuroblastoma with metastases to the brain presenting as refusal to move the left arm. The lesion initially appeared to be both a subdural and epidural hematoma on computed tomography of the head, but upon magnetic resonance imaging, was found to represent metastatic neuroblastoma. In pediatric patients with systemic symptoms and neurologic deficits, metastatic disease, such as neuroblastoma, should be included in the differential diagnosis and appropriate imaging should be obtained.

  12. Lapatinib potentiates cytotoxicity of  YM155 in neuroblastoma via inhibition of the ABCB1 efflux transporter.

    Science.gov (United States)

    Radic-Sarikas, Branka; Halasz, Melinda; Huber, Kilian V M; Winter, Georg E; Tsafou, Kalliopi P; Papamarkou, Theodore; Brunak, Søren; Kolch, Walter; Superti-Furga, Giulio

    2017-06-08

    Adverse side effects of cancer agents are of great concern in the context of childhood tumors where they can reduce the quality of life in young patients and cause life-long adverse effects. Synergistic drug combinations can lessen potential toxic side effects through lower dosing and simultaneously help to overcome drug resistance. Neuroblastoma is the most common cancer in infancy and extremely heterogeneous in clinical presentation and features. Applying a systematic pairwise drug combination screen we observed a highly potent synergy in neuroblastoma cells between the EGFR kinase inhibitor lapatinib and the anticancer compound YM155 that is preserved across several neuroblastoma variants. Mechanistically, the synergy was based on a lapatinib induced inhibition of the multidrug-resistance efflux transporter ABCB1, which is frequently expressed in resistant neuroblastoma cells, which allowed prolonged and elevated cytotoxicity of YM155. In addition, the drug combination (i.e. lapatinib plus YM155) decreased neuroblastoma tumor size in an in vivo model.

  13. Smooth muscle adaptation after intestinal transection and resection.

    Science.gov (United States)

    Thompson, J S; Quigley, E M; Adrian, T E

    1996-09-01

    Changes in motor function occur in the intestinal remnant after intestinal resection. Smooth muscle adaptation also occurs, particularly after extensive resection. The time course of these changes and their interrelationship are unclear. Our aim was to evaluate changes in canine smooth muscle structure and function during intestinal adaptation after transection and resection. Twenty-five dogs underwent either transection (N = 10), 50% distal resection (N = 10), or 50% proximal resection (N = 5). Thickness and length of the circular (CM) and longitudinal (LM) muscle layers were measured four and 12 weeks after resection. In vitro length-tension properties and response to a cholinergic agonist were studied in mid-jejunum and mid-ileum. Transection alone caused increased CM length in the jejunum proximal to the transection but did not affect LM length or muscle thickness. A 50% resection resulted in increased length of CM throughout the intestine and thickening of CM and LM near the anastomosis. Active tension of jejunal CM increased transiently four weeks after resection. Active tension in jejunal LM was decreased 12 weeks after transection and resection. Sensitivity of CM to carbachol was similar after transection and resection. It is concluded that: (1) Structural adaptation of both circular and longitudinal muscle occurs after intestinal resection. (2) This process is influenced by the site of the intestinal remnant. (3) Only minor and transient changes occur in smooth muscle function after resection. (4) Factors other than muscle adaptation are likely involved in the changes in motor function seen following massive bowel resection.

  14. PPAR Gamma in Neuroblastoma: The Translational Perspectives of Hypoglycemic Drugs

    Directory of Open Access Journals (Sweden)

    Serena Vella

    2016-01-01

    Full Text Available Neuroblastoma (NB is the most common and aggressive pediatric cancer, characterized by a remarkable phenotypic diversity and high malignancy. The heterogeneous clinical behavior, ranging from spontaneous remission to fatal metastatic disease, is attributable to NB biology and genetics. Despite major advances in therapies, NB is still associated with a high morbidity and mortality. Thus, novel diagnostic, prognostic, and therapeutic approaches are required, mainly to improve treatment outcomes of high-risk NB patients. Among neuroepithelial cancers, NB is the most studied tumor as far as PPAR ligands are concerned. PPAR ligands are endowed with antitumoral effects, mainly acting on cancer stem cells, and constitute a possible add-on therapy to antiblastic drugs, in particular for NB with unfavourable prognosis. While discussing clinical background, this review will provide a synopsis of the major studies about PPAR expression in NB, focusing on the potential beneficial effects of hypoglycemic drugs, thiazolidinediones and metformin, to reduce the occurrence of relapses as well as tumor regrowth in NB patients.

  15. Glycolysis-respiration relationships in a neuroblastoma cell line.

    Science.gov (United States)

    Swerdlow, Russell H; E, Lezi; Aires, Daniel; Lu, Jianghua

    2013-04-01

    Although some reciprocal glycolysis-respiration relationships are well recognized, the relationship between reduced glycolysis flux and mitochondrial respiration has not been critically characterized. We concomitantly measured the extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) of SH-SY5Y neuroblastoma cells under free and restricted glycolysis flux conditions. Under conditions of fixed energy demand ECAR and OCR values showed a reciprocal relationship. In addition to observing an expected Crabtree effect in which increasing glucose availability raised the ECAR and reduced the OCR, a novel reciprocal relationship was documented in which reducing the ECAR via glucose deprivation or glycolysis inhibition increased the OCR. Substituting galactose for glucose, which reduces net glycolysis ATP yield without blocking glycolysis flux, similarly reduced the ECAR and increased the OCR. We further determined how reduced ECAR conditions affect proteins that associate with energy sensing and energy response pathways. ERK phosphorylation, SIRT1, and HIF1a decreased while AKT, p38, and AMPK phosphorylation increased. These data document a novel intracellular glycolysis-respiration effect in which restricting glycolysis flux increases mitochondrial respiration. Since this effect can be used to manipulate cell bioenergetic infrastructures, this particular glycolysis-respiration effect can practically inform the development of new mitochondrial medicine approaches. Copyright © 2012 Elsevier B.V. All rights reserved.

  16. Molecular mechanism of action of opioids in human neuroblastoma cells

    International Nuclear Information System (INIS)

    Yu, V.C.K.

    1987-01-01

    A series of human neuroblastoma cell lines was screened for the presence of opioid receptor sites. Of these cell lines, SK-N-SH was found to express approximately 50,000 μ and 10,000 δ opioid receptor sites/cell. In vitro characterization revealed that the binding properties of these receptor sites closely resembled those of human and rodent brain. Phosphatidylinositol turnover as a potential second messenger system for the μ receptor was examined in SK-N-SH cells. Neurotransmitter receptor systems were determined in the three sub-clones of SK-N-SH cells. Cells of the SH-SY5Y line, a phenotypically stable subclone of SK-N-SH cells, were induced to differentiate by treatment with various inducing agents, and changes of several neurotransmitter receptor systems were determined. Nerve growth factor (NGF) and retinoic acid (RA) up-regulated, while dBcAMP down-regulated opioid receptor sites. [ 3 H]Dopamine uptake was slightly enhanced only in RA-treated cells. Strikingly, the efficacy of PGE 1 -stimulated accumulation of cAMP was enhanced by 15- to 30-fold upon RA treatment

  17. Neuroblastoma of the olfactory nerve - radiotherapeutic experiences with six patients

    International Nuclear Information System (INIS)

    Herzog, J.; Schmidt, B.; Petersen, D.; Schabet, M.

    1988-01-01

    Six patients with neuroblastomas of the olfactory nerve (aesthesioneuroblastoma) are presented who were irradiated between 1983 and 1986. Clinical manifestations, diagnostics, histology, therapy, and courses are compared and discused with regard to a survey of literature. An attempt is made to find out the value of radiotherapy in the treatment of this rare disease. In stage A (tumor restricted to the nasal cavity, 1 patient), a local tumor control of up to now 28 months could be achieved by a treatment combination of surgery and radiotherapy. A treatment consisting of surgery or radiotherapy alone should even in this stage only be performed in connection with a close follow-up because of the increased local recurrence risk. Five patients suffered from tumors of stage C (tumor extent beyond the paranasal sinuses). A good palliative effect was obtained temporarily by radiotherapy alone in three out of these patients showing large inoperable tumors and rapidly progressing clinical symptoms. A complete remission now lasting 16 months was achieved only in one patient by radical surgery with unilateral evisceration of orbit and homogenous postirradiation. In case of stage C tumors it is recommended to perform, if possible, a radical tumor excision with evisceration of orbit in case of unilateral manifestation in the orbit and a postirradiation applying a radical, largevolume technique. In order to reduce the risk of radiogenic cerebral necroses, it should be attempted to avoid dose maxima as they can occur when applying a combined ventro-dorsal and lateral irradiation technique. (orig./MG) [de

  18. Radiotherapy of the cephalic segment in patients with advanced neuroblastoma

    International Nuclear Information System (INIS)

    Weltman, Eduardo

    1995-01-01

    Although the treatment results have significantly improved for several pediatric malignant neoplasms, particularly Wilms's tumor, lymphomas and leukemia, in the last decade, the prognosis of the INSS, stage 4 neuroblastoma over one year one old patients remains poor. Even for the more advanced centers, using the more aggressive treatment schedules, such as bone marrow transplantation, the probability of a 2 year progression free interval varies from 6 to 50% and at 3 to 6 years, from 13 to 54%. Thereby, at least, 46 to 94% of these patients are expected to die due to the merciless neoplasm progression. The hypothesis here to be tested is regarding the impact of the cephalic irradiation on the outcome of stage 4 patients with skull metastasis at diagnosis. The end point was to establish, under the NEURO-III-85 protocol chemotherapy schedule, the possible benefit of this radiotherapy in preventing the cephalic recurrence, and its reflex on these patients total and diseases free survival. These results disclosed that the cephalic segment irradiation may prevent recurrences at this site. Unfortunately, the decrease in the cranial recurrence frequency did not affect either the disease free interval, or the total survival. The conclusion was that cephalic irradiation have the potential of avoiding these recurrences, without modifying the final outcome. This modality of radiotherapy must be reevaluated under more effective systemic treatments. (author)

  19. Neuroblastoma in early childhood: A rare case report and review of literature

    Directory of Open Access Journals (Sweden)

    Ritesh R Kalaskar

    2016-01-01

    Full Text Available Neuroblastoma is an extremely rare pediatric neoplasm whose prognosis becomes poor and poor as the age advances. It can be sporadic or nonfamilial in origin. It is primarily a tumor of abdominal origin from where it metastasis to lymph nodes, liver, intracranial and orbital sites, and central nervous system. There is no standard dental treatment protocol for the management of neuroblastoma due to its poor survival rate and rarity. However, dental treatment may follow the protocol of preventive and restorative. Surgicals should be performed under supervision as it may trigger metastasis. We report a rare case of neuroblastoma in a 3-year-old child presenting classical oral manifestations such as bilateral palatal swelling, rolled border ulcer on the posterior part of hard palate adjacent to primary molars, and bilateral proptosis.

  20. Long-term control of olfactory neuroblastoma in a dog treated with surgery and radiation therapy.

    Science.gov (United States)

    Gumpel, E; Moore, A S; Simpson, D J; Hoffmann, K L; Taylor, D P

    2017-07-01

    Olfactory neuroblastoma is a rare malignancy of the nasal cavity in dogs that is thought to arise from specialised sensory neuroendocrine olfactory cells derived from the neural crest. An 8-year-old dog was presented for reclusiveness and pacing. On CT and MRI, a contract-enhancing mass was disclosed within the rostral fossa, extending caudally from the cribriform plate into the left nasal sinus. Surgical excision was performed and the diagnosis was histological grade III (Hyams grading scheme) olfactory neuroblastoma. Based on human CT criteria this was high stage (modified Kadish stage C). Surgical excision was incomplete and was followed by curative-intent radiation therapy using a linear accelerator to a total dose of 48 Gy. The dog survived 20 months after diagnosis. Although olfactory neuroblastoma is a rare tumour in dogs, aggressive local therapy may allow for prolonged survival, even when the tumour is advanced. © 2017 Australian Veterinary Association.

  1. Iodine 131 labeled GD2 monoclonal antibody in the diagnosis and therapy of human neuroblastoma

    International Nuclear Information System (INIS)

    Cheung, N.K.V.; Miraldi, F.D.

    1988-01-01

    High dose marrow ablative therapy followed by autologous bone marrow transplantation (ABMT) has prolonged survival in patients with neuroblastoma. Total body and focal irradiation play an integral role in the overall treatment of this disease. The biological basis for radiation is the radiosensitivity and the lack of sublethal repair in neuroblastoma cells. However, radiation therapy has not by itself been adequate because of the usual widespread nature of neuroblastoma and the inability to achieve selective tumor versus normal tissue delivery, especially at multiple tumor sites. Monoclonal antibodies are agents selected for their specificity for human tumors. In vivo they have the ability of targeting selectively to occult metastases. This paper discusses how the availability of radioisotopes and the development of conjugation chemistries have greatly expanded the potentials of these antibodies

  2. PPARbeta agonists trigger neuronal differentiation in the human neuroblastoma cell line SH-SY5Y.

    Science.gov (United States)

    Di Loreto, S; D'Angelo, B; D'Amico, M A; Benedetti, E; Cristiano, L; Cinque, B; Cifone, M G; Cerù, M P; Festuccia, C; Cimini, A

    2007-06-01

    Neuroblastomas are pediatric tumors originating from immature neuroblasts in the developing peripheral nervous system. Differentiation therapies could help lowering the high mortality due to rapid tumor progression to advanced stages. Oleic acid has been demonstrated to promote neuronal differentiation in neuronal cultures. Herein we report on the effects of oleic acid and of a specific synthetic PPARbeta agonist on cell growth, expression of differentiation markers and on parameters responsible for the malignancy such as adhesion, migration, invasiveness, BDNF, and TrkB expression of SH-SY5Y neuroblastoma cells. The results obtained demonstrate that many, but not all, oleic acid effects are mediated by PPARbeta and support a role for PPARbeta in neuronal differentiation strongly pointing towards PPAR ligands as new therapeutic strategies against progression and recurrences of neuroblastoma.

  3. DNA replication and post-replication repair in U.V.-sensitive mouse neuroblastoma cells

    International Nuclear Information System (INIS)

    Lavin, M.F.; McCombe, P.; Kidson, C.

    1976-01-01

    Mouse neuroblastoma cells differentiated when grown in the absence of serum; differentiation was reversed on the addition of serum. Differentiated cells were more sensitive to U.V.-radiation than proliferating cells. Whereas addition of serum to differentiated neuroblastoma cells normally resulted in immediate, synchronous entry into S phase, irradiation just before the addition of serum resulted in a long delay in the onset of DNA replication. During this lag period, incorporated 3 H-thymidine appeared in the light density region of CsCl gradients, reflecting either repair synthesis or abortive replication. Post-replication repair (gap-filling) was found to be present in proliferating cells and at certain times in differentiated cells. It is suggested that the sensitivity of differentiated neuroblastoma cells to U.V.-radiation may have been due to ineffective post-replication repair or to deficiencies in more than one repair mechanism, with reduction in repair capacity beyond a critical threshold. (author)

  4. Multi-omic profiling of MYCN-amplified neuroblastoma cell-lines

    Directory of Open Access Journals (Sweden)

    Erik Dassi

    2015-12-01

    Full Text Available Neuroblastoma is the most common pediatric cancer, arising from the neural crest cells of the sympathetic nervous system. Its most aggressive subtype, characterized by the amplification of the MYCN oncogene, has a dismal prognosis and no effective treatment is available. Understanding the alterations induced by the tumor on the various layers of gene expression is therefore important for a complete characterization of this neuroblastoma subtype and for the discovery of new therapeutic opportunities. Here we describe the profiling of 13 MYCN-amplified neuroblastoma cell lines at the genome (copy number, transcriptome, translatome and miRome levels (GEO series GSE56654, GSE56552 and GSE56655. We provide detailed experimental and data analysis procedures by means of which we derived the results described in [1].

  5. 131I-MIBG in Neuroblastoma, is Not Simply the Uptake in the Primary Mass

    International Nuclear Information System (INIS)

    El-Maghraby, T.A.; Nasr, H.A.; Hassan, M.

    2003-01-01

    Neuroblastoma is the third most common malignancy of childhood. Nowadays. MlBG has become a central procedure for staging and defining extent and location of neuroblastoma tumors. The recommendations of the International Neuroblastoma Staging System (INSS) indicate that MlBG scintigraphy must be performed in patients with neuroblastoma at the time of initial staging and as a followup tool during therapy. Purpose: Of this study is to identify the role of 131 I M lBG scintigraphy in neuroblastoma patients and to correlate it with other diagnostic modalities for staging and follow up of neuroblastoma. Methods: The study was conducted on 26 patients provisionally diagnosed to have neuroblastoma. On histopathologic verification 5 of these 26 patients were re diagnosed as non-neuroblastoma. Since the study aims at assessing the diagnostic power of 131 I M IBG scan, these 5 cases were not excluded. The 21 histopathologically diagnosed as neuroblastoma were 11 patients in stage IV, 7 in stage III and 1 patient in each of stages I, 11 and IVS. Each. patient underwent a standard comprehensive diagnostic work up, Radiological imaging by conventional X-ray. ultrasound. CT and/or MRI was carried out. In all patients I3II M IBG scintigraphy was performed, among them 15 patients underwent additional 99m Tc-MDP bone scan as well. The 21 neuroblastoma patients were studied according to the results obtained from CT, MRI and 131 I M lBG scanning. The outcome demonstrated that CT and MR1 were able to detect lesions in 19 out of 2] patients; while in 2 patients no lesions were detected. 131 I M IBG scan showed actively functioning lesions in ] 6 out of the above] 9 patients. while in 3 patients MIBG scan was negative. There was no false positive result by 131 I M IBG scan. Accordingly. 131 1 M IBG is able to detect neuroblastoma lesions with an overall sensitivity of 84.2%. specificity of 100% and an accuracy of 85.7%. Detection of primary lesions by 131 I M lBG was significantly

  6. The nature of carrier localisation in polar and nonpolar InGaN/GaN quantum wells

    Energy Technology Data Exchange (ETDEWEB)

    Dawson, P., E-mail: philip.dawson@manchester.ac.uk [School of Physics and Astronomy, Photon Science Institute, University of Manchester, Manchester M13 9PL (United Kingdom); Schulz, S. [Photonics Theory Group, Tyndall National Institute, Dyke Parade, Cork (Ireland); Oliver, R. A.; Kappers, M. J.; Humphreys, C. J. [Department of Material Science and Metallurgy, 27 Charles Babbage Road, University of Cambridge, Cambridge CB3 0FS (United Kingdom)

    2016-05-14

    In this paper, we compare and contrast the experimental data and the theoretical predictions of the low temperature optical properties of polar and nonpolar InGaN/GaN quantum well structures. In both types of structure, the optical properties at low temperatures are governed by the effects of carrier localisation. In polar structures, the effect of the in-built electric field leads to electrons being mainly localised at well width fluctuations, whereas holes are localised at regions within the quantum wells, where the random In distribution leads to local minima in potential energy. This leads to a system of independently localised electrons and holes. In nonpolar quantum wells, the nature of the hole localisation is essentially the same as the polar case but the electrons are now coulombically bound to the holes forming localised excitons. These localisation mechanisms are compatible with the large photoluminescence linewidths of the polar and nonpolar quantum wells as well as the different time scales and form of the radiative recombination decay curves.

  7. Hysteroscopic Endometrial Resection in the Management of ...

    African Journals Online (AJOL)

    All women underwent hysteroscopic endometrial resection and 28 of them had hysteroscopic myomectomy. The success rate was 92.8% (65/70) after 2 years follow up. All the five women with failure of the procedure were younger ( 7 ...

  8. Expanded Endoscopic Endonasal Resection of Retrochiasmatic Craniopharyngioma.

    Science.gov (United States)

    Davanzo, Justin R; Goyal, Neerav; Zacharia, Brad E

    2018-02-01

    This video abstract demonstrates the use of the expanded endoscopic endonasal approach for the resection of a retrochiasmatic craniopharyngioma. These tumors are notoriously difficult to treat, and many approaches have been tried to facilitate safe and effective resection. The endoscopic endonasal approach has been increasingly utilized for selected sellar/suprasellar pathology. We present the case of a 39-year-old man who was found to have a cystic, partially calcified suprasellar mass consistent with a craniopharyngioma. To facilitate robust skull base repair, a vascularized nasoseptal flap was harvested. A wide sphenoidotomy was performed and the sella and tuberculum were exposed. After the dural opening and arachnoid dissection, the stalk was identified, merging seamlessly with the tumor capsule. The lesion was then internally debulked with the use of an ultrasonic aspirator. The capsule was then dissected off of the optic chiasm, thalamus, and hypothalamus. The cavity was inspected with an angled endoscope to ensure complete resection. A multilayered reconstruction was performed using autologous fascia lata, the previously harvested nasoseptal flap, and dural sealant. Postoperatively, the patient did have expected panhypopituitarism but remained neurologically intact and had improvement in his vision. In conclusion, this video demonstrates how an expanded endonasal approach can be used to safely resect a craniopharyngioma, even when in close proximity to delicate structures such as the optic chiasm. The link to the video can be found at: https://youtu.be/tahjHmrXhc4 .

  9. Resection methodology for PSP data processing: Recent ...

    Indian Academy of Sciences (India)

    M. Senthilkumar (Newgen Imaging) 1461 1996 Oct 15 13:05:22

    Abstract. PSP data processing, which primarily involves image alignment and image analysis, is a crucial element in obtaining accurate PSP results. There are two broad approaches to image alignment: the algebraic transformation technique, often called image-warping technique, and resection methodology, which uses ...

  10. What Keeps Postpulmonary Resection Patients in Hospital?

    Directory of Open Access Journals (Sweden)

    T Bardell

    2003-01-01

    Full Text Available BACKGROUND: Prolonged air leak (longer than three days was hypothesized to be the primary cause of extended hospital stays following pulmonary resection. Its effect on length of stay (LOS was compared with that of suboptimal pain control, nausea and vomiting, and other causes. Predictors of prolonged LOS and of prolonged air leaks were investigated.

  11. BLADDER NECK RESECTION WITH PRESERVATION OF ...

    African Journals Online (AJOL)

    Conclusion The complication of retrograde ejaculation in young patients who are in need of fertililty may be avoided by preservation of > 1 cm of the supramontanal part during bladder neck resection. La Résection du Col de Vessie avec Préservation de l'Ejaculation Antégrade Objectif Evaluer une nouvelle méthode de ...

  12. A rare indication for liver resection.

    Science.gov (United States)

    Popescu, I; Zamfir, R; Braşoveanu, V; Boroş, M; Herlea, V

    2005-01-01

    We present the rare case of a young female with a right upper abdomen tumoral mass and suffering abdominal discomfort. A combination of ultrasonography, computed tomography, magnetic resonance imaging and laparotomy was utilized to conclude a diagnosis of Riedel's lobe. Laparotomy and a resection of Riedel's lobe were selected as the correct therapeutic solutions.

  13. Single incision laparoscopic colorectal resection: Our experience

    Directory of Open Access Journals (Sweden)

    Chinnusamy Palanivelu

    2012-01-01

    Full Text Available Background: A prospective case series of single incision multiport laparoscopic colorectal resections for malignancy using conventional laparoscopic trocars and instruments is described. Materials and Methods: Eleven patients (seven men and four women with colonic or rectal pathology underwent single incision multiport laparoscopic colectomy/rectal resection from July till December 2010. Four trocars were placed in a single transumblical incision. The bowel was mobilized laparoscopically and vessels controlled intracorporeally with either intra or extracorporeal anastomosis. Results: Three patients had carcinoma in the caecum, one in the hepatic flexure, two in the rectosigmoid, one in the descending colon, two in the rectum and two had ulcerative pancolitis (one with high grade dysplasia and another with carcinoma rectum. There was no conversion to standard multiport laparoscopy or open surgery. The median age was 52 years (range 24-78 years. The average operating time was 130 min (range 90-210 min. The average incision length was 3.2 cm (2.5-4.0 cm. There were no postoperative complications. The average length of stay was 4.5 days (range 3-8 days. Histopathology showed adequate proximal and distal resection margins with an average lymph node yield of 25 nodes (range 16-30 nodes. Conclusion: Single incision multiport laparoscopic colorectal surgery for malignancy is feasible without extra cost or specialized ports/instrumentation. It does not compromise the oncological radicality of resection. Short-term results are encouraging. Long-term results are awaited.

  14. Outcome of colorectal cancer resection in octogenarians

    African Journals Online (AJOL)

    Colorectal cancer is predominantly a disease of the elderly. It is the second most common cancer in the UK and the third most common cause of cancer-related death.[1] Surgical resection, either for cure or palliation, remains the mainstay of treatment.[1,2]. Long-term survival is related to the extent of disease at diagnosis.

  15. Anaesthetic management of endoscopic resection of juvenile ...

    African Journals Online (AJOL)

    P Khanna, BR Ray, R Sinha, R Kumar, K Sikka, AC Singh ... We present the anaesthetic management of endoscopic resection of 14 JNAs, together with a review. ... Mean duration of surgery was 197.14 ± 77 minutes, and median blood loss ...

  16. Resection planning for robotic acoustic neuroma surgery

    Science.gov (United States)

    McBrayer, Kepra L.; Wanna, George B.; Dawant, Benoit M.; Balachandran, Ramya; Labadie, Robert F.; Noble, Jack H.

    2016-03-01

    Acoustic neuroma surgery is a procedure in which a benign mass is removed from the Internal Auditory Canal (IAC). Currently this surgical procedure requires manual drilling of the temporal bone followed by exposure and removal of the acoustic neuroma. This procedure is physically and mentally taxing to the surgeon. Our group is working to develop an Acoustic Neuroma Surgery Robot (ANSR) to perform the initial drilling procedure. Planning the ANSR's drilling region using pre-operative CT requires expertise and around 35 minutes' time. We propose an approach for automatically producing a resection plan for the ANSR that would avoid damage to sensitive ear structures and require minimal editing by the surgeon. We first compute an atlas-based segmentation of the mastoid section of the temporal bone, refine it based on the position of anatomical landmarks, and apply a safety margin to the result to produce the automatic resection plan. In experiments with CTs from 9 subjects, our automated process resulted in a resection plan that was verified to be safe in every case. Approximately 2 minutes were required in each case for the surgeon to verify and edit the plan to permit functional access to the IAC. We measured a mean Dice coefficient of 0.99 and surface error of 0.08 mm between the final and automatically proposed plans. These preliminary results indicate that our approach is a viable method for resection planning for the ANSR and drastically reduces the surgeon's planning effort.

  17. Mdm2 Deficiency Suppresses MYCN-Driven Neuroblastoma Tumorigenesis In Vivo

    Directory of Open Access Journals (Sweden)

    Zaowen Chen

    2009-08-01

    Full Text Available Neuroblastoma is derived from neural crest precursor components of the peripheral sympathetic nervous system and accounts for more than 15% of all pediatric cancer deaths. A clearer understanding of the molecular basis of neuroblastoma is required for novel therapeutic approaches to improve morbidity and mortality. Neuroblastoma is uniformly p53 wild type at diagnosis and must overcome p53-mediated tumor suppression during pathogenesis. Amplification of the MYCN oncogene correlates with the most clinically aggressive form of the cancer, and MDM2, a primary inhibitor of the p53 tumor suppressor, is a direct transcriptional target of, and positively regulated by, both MYCN and MYCC. We hypothesize that MDM2 contributes to MYCN-driven tumorigenesis helping to ameliorate p53-dependent apoptotic oncogenic stress during tumor initiation and progression. To study the interaction of MYCN and MDM2, we generated an Mdm2 haploinsufficient transgenic animal model of neuroblastoma. In Mdm2+/-MYCN transgenics, tumor latency and animal survival are remarkably extended, whereas tumor incidence and growth are reduced. Analysis of the Mdm2/p53 pathway reveals remarkable p53 stabilization counterbalanced by epigenetic silencing of the p19Arf gene in the Mdm2 haploinsufficient tumors. In human neuroblastoma xenograft models, conditional small interfering RNA-mediated knockdown of MDM2 in cells expressing wild-type p53 dramatically suppresses tumor growth in a p53-dependent manner. In summary, we provided evidence for a crucial role for direct inhibition of p53 by MDM2 and suppression of the p19ARF/p53 axis in neuroblastoma tumorigenesis, supporting the development of therapies targeting these pathways.

  18. Chemotherapy-Induced Apoptosis in a Transgenic Model of Neuroblastoma Proceeds Through p53 Induction

    Directory of Open Access Journals (Sweden)

    Louis Chesler

    2008-11-01

    Full Text Available Chemoresistance in neuroblastoma is a significant issue complicating treatment of this common pediatric solid tumor. MYCN-amplified neuroblastomas are infrequently mutated at p53 and are chemosensitive at diagnosis but acquire p53 mutations and chemoresistance with relapse. Paradoxically, Myc-driven transformation is thought to require apoptotic blockade. We used the TH-MYCN transgenic murine model to examine the role of p53-driven apoptosis on neuroblastoma tumorigenesis and the response to chemotherapy. Tumors formed with high penetrance and low latency in p53-haploinsufficient TH-MYCN mice. Cyclophosphamide (CPM induced a complete remission in p53 wild type TH-MYCN tumors, mirroring the sensitivity of childhood neuroblastoma to this agent. Treated tumors showed a prominent proliferation block, induction of p53 protein, and massive apoptosis proceeding through induction of the Bcl-2 homology domain-3-only proteins PUMA and Bim, leading to the activation of Bax and cleavage of caspase-3 and -9. Apoptosis induced by CPM was reduced in p53-haploinsufficient tumors. Treatment of MYCN-expressing human neuroblastoma cell lines with CPM induced apoptosis that was suppressible by siRNA to p53. Taken together, the results indicate that the p53 pathway plays a significant role in opposing MYCN-driven oncogenesis in a mouse model of neuroblastoma and that basal inactivation of the pathway is achieved in progressing tumors. This, in part, explains the striking sensitivity of such tumors to chemotoxic agents that induce p53-dependent apoptosis and is consistent with clinical observations that therapy-associated mutations in p53 are a likely contributor to the biology of tumors at relapse and secondarily mediate resistance to therapy.

  19. Codon 201Gly Polymorphic Type of the DCC Gene is Related to Disseminated Neuroblastoma

    Directory of Open Access Journals (Sweden)

    Xiao-Tang Kong

    2001-01-01

    Full Text Available The deleted in colorectal carcinoma (DCC gene is a potential tumor- suppressor gene on chromosome 18821.3. The relatively high frequency of loss of heterozygosity (LOH and loss of expression of this gene in neuroblastoma, especially in the advanced stages, imply the possibility of involvement of the DCC gene in progression of neuroblastoma. However, only few typical mutations have been identified in this gene, indicating that other possible mechanisms for the inactivation of this gene may exist. A polymorphic change (Arg to Gly at DCC codon 201 is related to advanced colorectal carcinoma and increases in the tumors with absent DCC protein expression. In order to understand whether this change is associated with the development or progression of neuroblastoma, we investigated codon 201 polymorphism of the DCC gene in 102 primary neuroblastomas by polymerase chain reaction single-strand conformation polymorphism. We found no missense or nonsense mutations, but a polymorphic change from CGA (Arg to GGA (Gly at codon 201 resulting in three types of polymorphism: codon 201Gly type, codon 201Arg/Gly type, and codon 201Arg type. The codon 201Gly type occurred more frequently in disseminated (stages IV and IVs neuroblastomas (72% than in localized (stages I, II, and III tumors (48% (P=.035, and normal controls (38% (P=.024. In addition, the codon 201Gly type was significantly more common in tumors found clinically (65% than in those found by mass screening (35% (P=.002. The results suggested that the codon 201Gly type of the DCC gene might be associated with a higher risk of disseminating neuroblastoma.

  20. Functional dissection of HOXD cluster genes in regulation of neuroblastoma cell proliferation and differentiation.

    Directory of Open Access Journals (Sweden)

    Yunhong Zha

    Full Text Available Retinoic acid (RA can induce growth arrest and neuronal differentiation of neuroblastoma cells and has been used in clinic for treatment of neuroblastoma. It has been reported that RA induces the expression of several HOXD genes in human neuroblastoma cell lines, but their roles in RA action are largely unknown. The HOXD cluster contains nine genes (HOXD1, HOXD3, HOXD4, and HOXD8-13 that are positioned sequentially from 3' to 5', with HOXD1 at the 3' end and HOXD13 the 5' end. Here we show that all HOXD genes are induced by RA in the human neuroblastoma BE(2-C cells, with the genes located at the 3' end being activated generally earlier than those positioned more 5' within the cluster. Individual induction of HOXD8, HOXD9, HOXD10 or HOXD12 is sufficient to induce both growth arrest and neuronal differentiation, which is associated with downregulation of cell cycle-promoting genes and upregulation of neuronal differentiation genes. However, induction of other HOXD genes either has no effect (HOXD1 or has partial effects (HOXD3, HOXD4, HOXD11 and HOXD13 on BE(2-C cell proliferation or differentiation. We further show that knockdown of HOXD8 expression, but not that of HOXD9 expression, significantly inhibits the differentiation-inducing activity of RA. HOXD8 directly activates the transcription of HOXC9, a key effector of RA action in neuroblastoma cells. These findings highlight the distinct functions of HOXD genes in RA induction of neuroblastoma cell differentiation.

  1. The Checkpoint Kinase 1 Inhibitor Prexasertib Induces Regression of Preclinical Models of Human Neuroblastoma.

    Science.gov (United States)

    Lowery, Caitlin D; VanWye, Alle B; Dowless, Michele; Blosser, Wayne; Falcon, Beverly L; Stewart, Julie; Stephens, Jennifer; Beckmann, Richard P; Bence Lin, Aimee; Stancato, Louis F

    2017-08-01

    Purpose: Checkpoint kinase 1 (CHK1) is a key regulator of the DNA damage response and a mediator of replication stress through modulation of replication fork licensing and activation of S and G 2 -M cell-cycle checkpoints. We evaluated prexasertib (LY2606368), a small-molecule CHK1 inhibitor currently in clinical testing, in multiple preclinical models of pediatric cancer. Following an initial assessment of prexasertib activity, this study focused on the preclinical models of neuroblastoma. Experimental Design: We evaluated the antiproliferative activity of prexasertib in a panel of cancer cell lines; neuroblastoma cell lines were among the most sensitive. Subsequent Western blot and immunofluorescence analyses measured DNA damage and DNA repair protein activation. Prexasertib was investigated in several cell line-derived xenograft mouse models of neuroblastoma. Results: Within 24 hours, single-agent prexasertib promoted γH2AX-positive double-strand DNA breaks and phosphorylation of DNA damage sensors ATM and DNA-PKcs, leading to neuroblastoma cell death. Knockdown of CHK1 and/or CHK2 by siRNA verified that the double-strand DNA breaks and cell death elicited by prexasertib were due to specific CHK1 inhibition. Neuroblastoma xenografts rapidly regressed following prexasertib administration, independent of starting tumor volume. Decreased Ki67 and increased immunostaining of endothelial and pericyte markers were observed in xenografts after only 6 days of exposure to prexasertib, potentially indicating a swift reduction in tumor volume and/or a direct effect on tumor vasculature. Conclusions: Overall, these data demonstrate that prexasertib is a specific inhibitor of CHK1 in neuroblastoma and leads to DNA damage and cell death in preclinical models of this devastating pediatric malignancy. Clin Cancer Res; 23(15); 4354-63. ©2017 AACR . ©2017 American Association for Cancer Research.

  2. Differential regulation of cyclin-dependent kinase inhibitors in neuroblastoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Qiao, Lan [Department of Pediatric Surgery, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Department of Pharmaceutical Sciences, Jilin University, Changchun 130021 (China); Paul, Pritha; Lee, Sora [Department of Pediatric Surgery, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Qiao, Jingbo [Department of Pediatric Surgery, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Wang, Yongsheng [Department of Pharmaceutical Sciences, Jilin University, Changchun 130021 (China); Chung, Dai H., E-mail: dai.chung@vanderbilt.edu [Department of Pediatric Surgery, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, TN 37232 (United States)

    2013-05-31

    Highlights: •GRP-R signaling differentially regulated the expression of p21 and p27. •Silencing GRP/GRP-R downregulated p21, while p27 expression was upregulated. •Inhibition of GRP/GRP-R signaling enhanced PTEN expression, correlative to the increased expression of p27. •PTEN and p27 co-localized in cytoplasm and silencing PTEN decreased p27 expression. -- Abstract: Gastrin-releasing peptide (GRP) and its receptor (GRP-R) are highly expressed in undifferentiated neuroblastoma, and they play critical roles in oncogenesis. We previously reported that GRP activates the PI3K/AKT signaling pathway to promote DNA synthesis and cell cycle progression in neuroblastoma cells. Conversely, GRP-R silencing induces cell cycle arrest. Here, we speculated that GRP/GRP-R signaling induces neuroblastoma cell proliferation via regulation of cyclin-dependent kinase (CDK) inhibitors. Surprisingly, we found that GRP/GRP-R differentially induced expressions of p21 and p27. Silencing GRP/GRP-R decreased p21, but it increased p27 expressions in neuroblastoma cells. Furthermore, we found that the intracellular localization of p21 and p27 in the nuclear and cytoplasmic compartments, respectively. In addition, we found that GRP/GRP-R silencing increased the expression and accumulation of PTEN in the cytoplasm of neuroblastoma cells where it co-localized with p27, thus suggesting that p27 promotes the function of PTEN as a tumor suppressor by stabilizing PTEN in the cytoplasm. GRP/GRP-R regulation of CDK inhibitors and tumor suppressor PTEN may be critical for tumoriogenesis of neuroblastoma.

  3. In vitro photothermal destruction of neuroblastoma cells using carbon nanotubes conjugated with GD2 monoclonal antibody

    International Nuclear Information System (INIS)

    Wang, Chung-Hao; Huang, Yao-Jhang; Chang, Chia-Wei; Peng, Ching-An; Hsu, Wen-Ming

    2009-01-01

    Despite aggressive multimodality therapy, most neuroblastoma-bearing patients relapse and survival rate remains poor. Exploration of alternative therapeutic modalities is needed. Carbon nanotubes (CNTs), revealing optical absorbance in the near-infrared region, warrant their merits in photothermal therapy. In order to specifically target disialoganglioside (GD2) overexpressed on the surface of neuroblastoma stNB-V1 cells, GD2 monoclonal antibody (anti-GD2) was conjugated to acidified CNTs. To examine the fate of anti-GD2 bound CNTs after incubation with stNB-V1 cells, rhodamine B was labeled on carboxylated CNTs functionalized with and without anti-GD2. Our results illustrated that anti-GD2-linked CNTs were extensively internalized by neuroblastoma cells via GD2-mediated endocytosis. In addition, we showed that anti-GD2 bound CNTs were not ingested by PC12 cells without GD2 expression. After anti-GD2 conjugated CNTs were incubated with neuroblastoma cells for 6 h and endocytosed by the cells, CNT-laden neuroblastoma cells were further irradiated with an 808 nm near-infrared (NIR) laser with intensity ramping from 0.6 to 6 W cm -2 for 10 min which was then maintained at 6 W cm -2 for an additional 5 min. Post-NIR laser exposure, and after being examined by calcein-AM dye, stNB-V1 cells were all found to undergo necrosis, while non-GD2 expressing PC12 cells all remained viable. Based on the in vitro study, CNTs bound with anti-GD2 have the potential to be utilized as a therapeutic thermal coupling agent that generates heat sufficient to selectively kill neuroblastoma cells under NIR laser light exposure.

  4. Differential regulation of cyclin-dependent kinase inhibitors in neuroblastoma cells

    International Nuclear Information System (INIS)

    Qiao, Lan; Paul, Pritha; Lee, Sora; Qiao, Jingbo; Wang, Yongsheng; Chung, Dai H.

    2013-01-01

    Highlights: •GRP-R signaling differentially regulated the expression of p21 and p27. •Silencing GRP/GRP-R downregulated p21, while p27 expression was upregulated. •Inhibition of GRP/GRP-R signaling enhanced PTEN expression, correlative to the increased expression of p27. •PTEN and p27 co-localized in cytoplasm and silencing PTEN decreased p27 expression. -- Abstract: Gastrin-releasing peptide (GRP) and its receptor (GRP-R) are highly expressed in undifferentiated neuroblastoma, and they play critical roles in oncogenesis. We previously reported that GRP activates the PI3K/AKT signaling pathway to promote DNA synthesis and cell cycle progression in neuroblastoma cells. Conversely, GRP-R silencing induces cell cycle arrest. Here, we speculated that GRP/GRP-R signaling induces neuroblastoma cell proliferation via regulation of cyclin-dependent kinase (CDK) inhibitors. Surprisingly, we found that GRP/GRP-R differentially induced expressions of p21 and p27. Silencing GRP/GRP-R decreased p21, but it increased p27 expressions in neuroblastoma cells. Furthermore, we found that the intracellular localization of p21 and p27 in the nuclear and cytoplasmic compartments, respectively. In addition, we found that GRP/GRP-R silencing increased the expression and accumulation of PTEN in the cytoplasm of neuroblastoma cells where it co-localized with p27, thus suggesting that p27 promotes the function of PTEN as a tumor suppressor by stabilizing PTEN in the cytoplasm. GRP/GRP-R regulation of CDK inhibitors and tumor suppressor PTEN may be critical for tumoriogenesis of neuroblastoma

  5. Prematurity reduces functional adaptation to intestinal resection in piglets

    DEFF Research Database (Denmark)

    Aunsholt, Lise; Thymann, Thomas; Qvist, Niels

    2015-01-01

    Background: Necrotizing enterocolitis and congenital gastrointestinal malformations in infants often require intestinal resection, with a subsequent risk of short bowel syndrome (SBS). We hypothesized that immediate intestinal adaptation following resection of the distal intestine with placement ...

  6. Learning Transurethral Resection of the Prostate: A Comparison of ...

    African Journals Online (AJOL)

    2018-01-30

    Jan 30, 2018 ... benign prostate enlargement (BPE) are of limited use in the resource‑poor ... trans‑urethral resection of the prostate, resected weight, retropubic prostatectomy ..... digital rectal examination and total prostate specific antigen.

  7. Comparison of radionuclide bone scan with radiographic skeletal survey in detecting metastases in neuroblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Tani, G.; Lucchi, A.; Pisi, P.; Boriani, F.; De Florio, L.; Turba, E.; Mancini, A.F.; Marchi, N.; Rossi, M.

    1987-10-01

    Neuroblastoma (NBL) with bone metastasis is in its IV (fourth) stage of development. In this study we discuss the radiological and scintigraphic data of 25 patients with neuroblastoma in the IV stage at diagnosis. All the patients had undergone a radiological examination of the whole skeleton and a bone scintigraphy. The aim of this work is to compare the sensitivity of the two methods. The authors conclude that both the examinations are important and complementary to define the IV stage of the disease to avoid underevaluations.

  8. Comparison of radionuclide bone scan with radiographic skeletal survey in detecting metastases in neuroblastoma

    International Nuclear Information System (INIS)

    Tani, G.; Lucchi, A.; Pisi, P.; Boriani, F.; De Florio, L.; Turba, E.; Mancini, A.F.; Marchi, N.; Rossi, M.

    1987-01-01

    Neuroblastoma (NBL) with bone metastasis is in its IV (fourth) stage of development. In this study we discuss the radiological and scintigraphic data of 25 patients with neuroblastoma in the IV stage at diagnosis. All the patients had undergone a radiological examination of the whole skeleton and a bone scintigraphy. The aim of this work is to compare the sensitivity of the two methods. The authors conclude that both the examinations are important and complementary to define the IV stage of the disease to avoid underevaluations. (orig.) [de

  9. Imaging defined risk factors in neuroblastoma -guidelines for optimising imaging interpretations

    International Nuclear Information System (INIS)

    Valchev, G.; Balev, B.

    2017-01-01

    Neuroblastoma is the most frequent extracranial tumor in children, arising from the primitive sympathetic cells and the adrenal medulla. Two separate mutually complementing staging systems exist - INSS and INRGSS - one is based on post-operative findings, the other - on pre-treatment imaging. INRGSS consists of a list of 20 separate imaging defined risk factors (IDRF), the presence of which could alter the treatment plan. Radiologists need to be aware of certain intricacies in interpreting the individual IDRFs in order to optimise clinical decision-making. Key words: neuroblastoma. imaging defined risk factors (IDRF). interpretation guidelines [bg

  10. Human perception of indoor environment generated by chilled ceiling combined with mixing ventilation or localised chilled beam under cooling mode

    DEFF Research Database (Denmark)

    Bolashikov, Zhecho Dimitrov; Nygaard, Linette; Uth, Simon C.

    2014-01-01

    Experiments with 24 subjects were performed to study and compare the human perception of the indoor environment under summer conditions generated by a chilled ceiling combined with overhead mixing ventilation and localised chilled beam. The experiments were performed in an experimental chamber (4....../s and 16 0C. The localised chilled beam was installed over the workstation placed by the simulated window. During the experiment the subjects were delegated control over the primary flow rate supplied by the localised chilled beam. The whole exposure lasted 2 hours with 30 min of acclimatisation before...

  11. [Laparoscopic resection of the sigmoid colon for the diverticular disease].

    Science.gov (United States)

    Vrbenský, L; Simša, J

    2013-07-01

    Laparoscopic resection of the sigmoid colon for diverticular disease is nowadays a fully accepted alternative to traditional open procedures. The aim of this work is to summarize the indications, advantages and risks of laparoscopic sigmoid resection for diverticular disease. Review of the literature and recent findings concerning the significance of laparoscopic resection for diverticulosis of the sigmoid colon. The article presents the indications, risks, techniques and perioperative care in patients after laparoscopic resection of the sigmoid colon for diverticular disease.

  12. Radiotherapy of the cephalic segment in patients with advanced neuroblastoma; Radioterapia do segmento cefalico em pacientes portadores de neuroblastoma avancado

    Energy Technology Data Exchange (ETDEWEB)

    Weltman, Eduardo

    1995-07-01

    Although the treatment results have significantly improved for several pediatric malignant neoplasms, particularly Wilms's tumor, lymphomas and leukemia, in the last decade, the prognosis of the INSS, stage 4 neuroblastoma over one year one old patients remains poor. Even for the more advanced centers, using the more aggressive treatment schedules, such as bone marrow transplantation, the probability of a 2 year progression free interval varies from 6 to 50% and at 3 to 6 years, from 13 to 54%. Thereby, at least, 46 to 94% of these patients are expected to die due to the merciless neoplasm progression. The hypothesis here to be tested is regarding the impact of the cephalic irradiation on the outcome of stage 4 patients with skull metastasis at diagnosis. The end point was to establish, under the NEURO-III-85 protocol chemotherapy schedule, the possible benefit of this radiotherapy in preventing the cephalic recurrence, and its reflex on these patients total and diseases free survival. These results disclosed that the cephalic segment irradiation may prevent recurrences at this site. Unfortunately, the decrease in the cranial recurrence frequency did not affect either the disease free interval, or the total survival. The conclusion was that cephalic irradiation have the potential of avoiding these recurrences, without modifying the final outcome. This modality of radiotherapy must be reevaluated under more effective systemic treatments. (author)

  13. Ifosfamide in previously untreated disseminated neuroblastoma. Results of Study 3A of the European Neuroblastoma Study Group.

    Science.gov (United States)

    Kellie, S J; De Kraker, J; Lilleyman, J S; Bowman, A; Pritchard, J

    1988-05-01

    A prospective study of the effectiveness of ifosfamide as a single agent in the management of previously untreated patients with Evans stage IV neuroblastoma was undertaken. Eighteen children aged more than 1 year were treated with ifosfamide (IFX) 3 g/m2 daily for 2 days immediately after diagnosis and 3 weeks later. Treatment was continued with combination chemotherapy using vincristine, cyclophosphamide, cisplatinum and etoposide (OPEC) or a variant. Mesna (2-mercaptoethane sulphonate) was given to all patients during IFX treatment to prevent urotoxicity. Eight of the 18 patients (44%) responded to IFX. Nine had greater than 66% reduction in baseline tumor volume. Of 15 evaluable patients with raised pre-treatment urinary catecholamine excretion, six (40%) achieved greater than 50% reduction in pretreatment levels. Two of 10 patients evaluable for bone marrow response had complete clearance. Toxicity was mild in all patients. Upon completing 'first line' therapy, only four patients (22%) achieved a good partial remission (GPR) or complete response (CR). Median survival was 11 months. There was a lower rate of attaining GPR and shortened median survival in patients receiving phase II IFX before OPEC or variant, compared to patients with similar pre-treatment characteristics treated with OPEC from diagnosis in an earlier study.

  14. Radiotherapy of the cephalic segment in patients with advanced neuroblastoma; Radioterapia do segmento cefalico em pacientes portadores de neuroblastoma avancado

    Energy Technology Data Exchange (ETDEWEB)

    Weltman, Eduardo

    1995-07-01

    Although the treatment results have significantly improved for several pediatric malignant neoplasms, particularly Wilms's tumor, lymphomas and leukemia, in the last decade, the prognosis of the INSS, stage 4 neuroblastoma over one year one old patients remains poor. Even for the more advanced centers, using the more aggressive treatment schedules, such as bone marrow transplantation, the probability of a 2 year progression free interval varies from 6 to 50% and at 3 to 6 years, from 13 to 54%. Thereby, at least, 46 to 94% of these patients are expected to die due to the merciless neoplasm progression. The hypothesis here to be tested is regarding the impact of the cephalic irradiation on the outcome of stage 4 patients with skull metastasis at diagnosis. The end point was to establish, under the NEURO-III-85 protocol chemotherapy schedule, the possible benefit of this radiotherapy in preventing the cephalic recurrence, and its reflex on these patients total and diseases free survival. These results disclosed that the cephalic segment irradiation may prevent recurrences at this site. Unfortunately, the decrease in the cranial recurrence frequency did not affect either the disease free interval, or the total survival. The conclusion was that cephalic irradiation have the potential of avoiding these recurrences, without modifying the final outcome. This modality of radiotherapy must be reevaluated under more effective systemic treatments. (author)

  15. Can immediate second resection be an alternative to standardized second transurethral resection of bladder tumors?

    Directory of Open Access Journals (Sweden)

    Engin Doğantekin

    2016-03-01

    Full Text Available This study analyzed the impact of an immediate second transurethral resection of bladder tumor (TURBT protocol on residual tumor status at the initial TURBT session and the recurrence rate in the primary resection area. We prospectively evaluated and randomized 47 consecutive patients who underwent TURBT sessions for bladder cancer. In accordance with the inclusion criteria, of the 47 consecutive patients, 19 (Group I underwent immediate second resection of the tumor bed after complete TUR and 28 (Group II did not. After standard TURBT, Group I underwent a second cystoscopy and resection of the bed of the tumor or an ignored tumor, which was performed by a different urologist. After 4–6 weeks, delayed second TURB was performed, and all pathological results were evaluated. Tumors were detected in two patients during the immediate second resection. Of these, one was a misdiagnosed tumor, whereas the other was diagnosed at the bed of the tumor by pathological examination. Tumors were detected in nine patients at the delayed second TURB, of which only one was part of Group I, while the others were part of Group II (p = 0.04. The results of this study demonstrated that residual tumors may remain after initial TURB, either in the tumor bed or in a different location within the bladder. Although this was a pilot study enrolling only a small number of patients, our initial results supported the assertion that immediate second resection can be an alternative to standard second TURBT.

  16. Etoposide-induced apoptosis in murine neuroblastoma (N2A cells infected with Paramyxoviruses Apoptose induzida por etoposídeo em células de neuroblastoma murino (N2A infectadas por paramixovírus

    Directory of Open Access Journals (Sweden)

    L. Moro

    2003-02-01

    Full Text Available The present study aimed to determine whether measles virus can induce apoptosis in murine neuroblastoma cells and the behavior of these cells under acute infection with measles virus or persistent infection with canine distemper virus upon treatment with etoposide. Measles virus induced necrosis in murine neuroblastoma cells. Canine distemper virus-persistent infection did not alter murine neuroblastoma cells behavior when treated with etoposide.O presente trabalho foi realizado tendo como objetivo determinar se o vírus de sarampo induz apoptose em células de neuroblastoma murino e avaliar o comportamento de células de neuroblastoma murino agudamente infectadas com vírus do sarampo ou persistentemente infectadas com o vírus da cinomose canina quando tratadas com etoposídeo. A infecção pelo vírus de sarampo induziu principalmente necrose em células de neuroblastoma murino. A infecção persistente pelo vírus de cinomose canina não alterou o comportamento de células de neuroblastoma murino tratadas com etoposídeo.

  17. Augmented reality in bone tumour resection: An experimental study.

    Science.gov (United States)

    Cho, H S; Park, Y K; Gupta, S; Yoon, C; Han, I; Kim, H-S; Choi, H; Hong, J

    2017-03-01

    We evaluated the accuracy of augmented reality (AR)-based navigation assistance through simulation of bone tumours in a pig femur model. We developed an AR-based navigation system for bone tumour resection, which could be used on a tablet PC. To simulate a bone tumour in the pig femur, a cortical window was made in the diaphysis and bone cement was inserted. A total of 133 pig femurs were used and tumour resection was simulated with AR-assisted resection (164 resection in 82 femurs, half by an orthropaedic oncology expert and half by an orthopaedic resident) and resection with the conventional method (82 resection in 41 femurs). In the conventional group, resection was performed after measuring the distance from the edge of the condyle to the expected resection margin with a ruler as per routine clinical practice. The mean error of 164 resections in 82 femurs in the AR group was 1.71 mm (0 to 6). The mean error of 82 resections in 41 femurs in the conventional resection group was 2.64 mm (0 to 11) (p Augmented reality in bone tumour resection: An experimental study. Bone Joint Res 2017;6:137-143. © 2017 Cho et al.

  18. Short-term outcomes following laparoscopic resection for colon cancer.

    LENUS (Irish Health Repository)

    Kavanagh, Dara O

    2011-03-01

    Laparoscopic resection for colon cancer has been proven to have a similar oncological efficacy compared to open resection. Despite this, it is performed by a minority of colorectal surgeons. The aim of our study was to evaluate the short-term clinical, oncological and survival outcomes in all patients undergoing laparoscopic resection for colon cancer.

  19. Une localisation exceptionnelle de la tuberculose vertébrale Mal de Pott sous-occipital

    Science.gov (United States)

    Yahyaoui, Sana; Majdoub, Senda; Zaghouani, Houneida; Fradj, Hosni Ben; Bakir, Dejla; Bouajina, Elyes; Kraiem, Chakib

    2013-01-01

    Le mal de Pott est la forme la plus commune de la tuberculose osseuse touchant essentiellement le rachis dorso-lombaire. La localisation sous-occipitale reste exceptionnelle. Le diagnostic de cette entité est le plus souvent tardif ce qui expose à des complications graves. Les radiographies standard ne sont parlantes qu’à un stade tardif de la maladie, d'où l'intérêt de l'imagerie moderne notamment la tomodensitométrie (TDM) et l'imagerie par résonance magnétique (IRM) qui permettent un diagnostic précoce. Nous rapportons un nouveau cas de tuberculose sous-occipitale. Le diagnostic était posé sur l'imagerie en coupe et confirmé histologiquement à la biopsie transorale. Sont rappelés les aspects en imagerie de cette localisation particulière du mal de Pott. PMID:23819005

  20. Flow in a circular expansion pipe flow: effect of a vortex perturbation on localised turbulence

    Energy Technology Data Exchange (ETDEWEB)

    Selvam, Kamal; Peixinho, Jorge [Laboratoire Ondes Milieux Complexes, CNRS and Université du Havre, F-76600 Le Havre (France); Willis, Ashley P, E-mail: jorge.peixinho@univ-lehavre.fr [School of Mathematics and Statistics, University of Sheffield, Sheffield S3 7RH (United Kingdom)

    2016-12-15

    We report the results of three-dimensional direct numerical simulations for incompressible viscous fluid in a circular pipe flow with a sudden expansion. At the inlet, a parabolic velocity profile is applied together with a finite amplitude perturbation in the form of a vortex with its axis parallel to the axis of the pipe. At sufficiently high Reynolds numbers the recirculation region breaks into a turbulent patch that changes position axially, depending on the strength of the perturbation. This vortex perturbation is believed to produce a less abrupt transition than in previous studies, which applied a tilt perturbation, as the localised turbulence is observed via the formation of a wavy structure at a low order azimuthal mode, which resembles an optimally amplified perturbation. For large vortex amplitude, the localised turbulence remains at a constant axial position. It is further investigated using proper orthogonal decomposition, which indicates that the centre region close to the expansion is highly energetic. (paper)